A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Science Immunology

Volumn 3, Issue 24, 2018, Pages

  Béziat, Vivien ^a,b   Li, Juan ^c   Lin, Jian Xin ^d   Ma, Cindy S ^e,f   Li, Peng ^d   Bousfiha, Aziz ^g   Pellier, Isabelle ^h   Zoghi, Samaneh ^i,j,k   Baris, Safa ^l   Keles, Sevgi ^m   Gray, Paul ^f,n   Du, Ning ^d   Wang, Yi ^a,b   Zerbib, Yoann ^a,b   Lévy, Romain ^a,b   Leclercq, Thibaut ^a,b   About, Frédégonde ^a,b   Lim, Ai Ing ^o,p   Rao, Geetha ^e   Payne, Kathryn ^e   Pelham, Simon J ^e,f   Avery, Danielle T ^e   Deenick, Elissa K ^e,f   Pillay, Bethany ^e,f   Chou, Janet ^q,r   Guery, Romain ^a,b,s   Belkadi, Aziz ^a,b   Guérin, Antoine ^a,b   Migaud, Mélanie ^a,b   Rattina, Vimel ^a,b   Ailal, Fatima ^g   Benhsaien, Ibtihal ^g   Bouaziz, Matthieu ^a,b   Habib, Tanwir ^t   Chaussabel, Damien ^t   Marr, Nico ^t   El Benna, Jamel ^u   Grimbacher, Bodo ^v   Wargon, Orli ⁿ   Bustamante, Jacinta ^a,b,c,s   Boisson, Bertrand ^a,b,c   Müller Fleckenstein, Ingrid ^w   Fleckenstein, Bernhard ^w   Chandesris, Marie Olivia ^s   Titeux, Matthias ^a,b   Fraitag, Sylvie ^s   Alyanakian, Marie Alexandra ^s   Leruez Ville, Marianne ^b,s   Picard, Capucine ^b,s   Meyts, Isabelle ^x   Di Santo, James P ^o,p   Hovnanian, Alain ^a,b,s   Somer, Ayper ^y   Ozen, Ahmet ^l   Rezaei, Nima ^i,j,k   Chatila, Talal A ^q,r   Abel, Laurent ^a,b,c   Leonard, Warren J ^d   Tangye, Stuart G ^e,f   Puel, Anne ^a,b,c   Casanova, Jean Laurent ^a,b,c,s,z   more..

^a IMAGINE INSTITUTE   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c ROCKEFELLER UNIVERSITY   (United States)

^d NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^e GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^f UNIVERSITY OF NEW SOUTH WALES   (Australia)

^g HASSAN II UNIVERSITY   (Morocco)

^h ANGERS UNIVERSITY HOSPITAL   (France)

ⁱ TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^j UNIVERSAL SCIENTIFIC EDUCATION AND RESEARCH NETWORK USERN   (Iran)

^k TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^l MARMARA UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

^m NECMETTIN ERBAKAN UNIVERSITY   (Turkey)

ⁿ SYDNEY CHILDREN'S HOSPITAL   (Australia)

^o INSTITUT PASTEUR   (France)

^p INSTITUT PASTEUR   (France)

^q BOSTON CHILDREN S HOSPITAL   (United States)

^r HARVARD MEDICAL SCHOOL   (United States)

^s HÔPITAL NECKER ENFANTS MALADES   (France)

^t SIDRA MEDICAL AND RESEARCH CENTER   (Qatar)

^u CENTRE DE RECHERCHE SUR L INFLAMMATION   (France)

^v UNIVERSITY OF FREIBURG   (Germany)

^w UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^x UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^y ISTANBUL UNIVERSITY   (Turkey)

^z HOWARD HUGHES MEDICAL INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; STAT3 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ZNF341; UNCLASSIFIED DRUG; CYTOKINE; IMMUNOGLOBULIN E; STAT3 PROTEIN, HUMAN; ZINC FINGER PROTEIN;

ARTICLE; CELL COUNT; CLINICAL ARTICLE; CONTROLLED STUDY; DNA BINDING; GENE FUNCTION; GENE LOSS; GENE MUTATION; HUMAN; HUMAN CELL; HYPER IGE SYNDROME; LYMPHOCYTE; MEMORY CELL; PRIORITY JOURNAL; PROMOTER REGION; TH17 CELL; TH2 CELL; ADOLESCENT; ADULT; BLOOD; CELL DIFFERENTIATION; CELL NUCLEUS; CONSANGUINITY; EXON; FEMALE; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; HOMOZYGOTE; IMMUNOLOGY; LOSS OF FUNCTION MUTATION; LYMPHOCYTE COUNT; MALE; METABOLISM; MIDDLE AGED; PEDIGREE; RECESSIVE GENE; WHOLE EXOME SEQUENCING; YOUNG ADULT;

ADOLESCENT; ADULT; CELL DIFFERENTIATION; CELL NUCLEUS; CONSANGUINITY; CYTOKINES; EXONS; FEMALE; GENE EXPRESSION REGULATION; GENES, RECESSIVE; HOMOZYGOTE; HUMANS; IMMUNOGLOBULIN E; JOB SYNDROME; LOSS OF FUNCTION MUTATION; LYMPHOCYTE COUNT; MALE; MIDDLE AGED; PEDIGREE; PROMOTER REGIONS, GENETIC; RNA, MESSENGER; STAT3 TRANSCRIPTION FACTOR; TH17 CELLS; TH2 CELLS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; WHOLE EXOME SEQUENCING; YOUNG ADULT; ZINC FINGERS;

EID: 85052886349     PISSN: None     EISSN: 24709468     Source Type: Journal    
DOI: 10.1126/sciimmunol.aat4956     Document Type: Article

References (84)

1. S. D. Davis, J. Schaller, R. J. Wedgwood, Job’s syndrome. Recurrent, “cold”, staphylococcal abscesses. Lancet 287, 1013–1015 (1966).
2. R. H. Buckley, B. B. Wray, E. Z. Belmaker, Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 49, 59–70 (1972).
3. B. Grimbacher, S. M. Holland, J. I. Gallin, F. Greenberg, S. C. Hill, H. L. Malech, J. A. Miller, A. C. O’Connell, J. M. Puck, Hyper-IgE syndrome with recurrent infections—An autosomal dominant multisystem disorder. N. Engl. J. Med. 340, 692–702 (1999).
4. M.-O. Chandesris, A. Azarine, K.-T. Ong, S. Taleb, P. Boutouyrie, E. Mousseaux, M. Romain, E. Bozec, S. Laurent, N. Boddaert, C. Thumerelle, I. Tillie-Leblond, C. Hoarau, Y. Lebranchu, N. Aladjidi, F. Tron, V. Barlogis, G. Body, M. Munzer, R. Jaussaud, F. Suarez, O. Clément, O. Hermine, A. Tedgui, O. Lortholary, C. Picard, Z. Mallat, A. Fischer, Frequent and widespread vascular abnormalities in human signal transducer and activator of transcription 3 deficiency. Circ. Cardiovasc. Genet. 5, 25–34 (2012).
5. D. T. Avery, E. K. Deenick, C. S. Ma, S. Suryani, N. Simpson, G. Y. Chew, T. D. Chan, U. Palendira, J. Bustamante, S. Boisson-Dupuis, S. Choo, K. E. Bleasel, J. Peake, C. King, M. A. French, D. Engelhard, S. Al-Hajjar, S. Al-Muhsen, K. Magdorf, J. Roesler, P. D. Arkwright, P. Hissaria, D. S. Riminton, M. Wong, R. Brink, D. A. Fulcher, J.-L. Casanova, M. C. Cook, S. G. Tangye, B cell–intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. J. Exp. Med. 207, 155–171 (2010).
6. Y. Minegishi, M. Saito, S. Tsuchiya, I. Tsuge, H. Takada, T. Hara, N. Kawamura, T. Ariga, S. Pasic, O. Stojkovic, A. Metin, H. Karasuyama, Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448, 1058–1062 (2007).
7. M.-O. Chandesris, I. Melki, A. Natividad, A. Puel, C. Fieschi, L. Yun, C. Thumerelle, E. Oksenhendler, D. Boutboul, C. Thomas, C. Hoarau, Y. Lebranchu, J.-L. Stephan, C. Cazorla, N. Aladjidi, M. Micheau, F. Tron, A. Baruchel, V. Barlogis, G. Palenzuela, C. Mathey, S. Dominique, G. Body, M. Munzer, F. Fouyssac, R. Jaussaud, B. Bader-Meunier, N. Mahlaoui, S. Blanche, M. Debré, M. Le Bourgeois, V. Gandemer, N. Lambert, V. Grandin, S. Ndaga, C. Jacques, C. Harre, M. Forveille, M.-A. Alyanakian, A. Durandy, C. Bodemer, F. Suarez, O. Hermine, O. Lortholary, J.-L. Casanova, A. Fischer, C. Picard, Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: Molecular, cellular, and clinical features from a French national survey. Medicine 91, e1–e19 (2012).
8. S. M. Holland, F. R. DeLeo, H. Z. Elloumi, A. P. Hsu, G. Uzel, N. Brodsky, A. F. Freeman, A. Demidowich, J. Davis, M. L. Turner, V. L. Anderson, D. N. Darnell, P. A. Welch, D. B. Kuhns, D. M. Frucht, H. L. Malech, J. I. Gallin, S. D. Kobayashi, A. R. Whitney, J. M. Voyich, J. M. Musser, C. Woellner, A. A. Schäffer, J. M. Puck, B. Grimbacher, STAT3 mutations in the hyper-IgE syndrome. N. Engl. J. Med. 357, 1608–1619 (2007).
9. E. D. Renner, S. Rylaarsdam, S. Aňover-Sombke, A. L. Rack, J. Reichenbach, J. C. Carey, Q. Zhu, A. F. Jansson, J. Barboza, L. F. Schimke, M. F. Leppert, M. M. Getz, R. A. Seger, H. R. Hill, B. H. Belohradsky, T. R. Torgerson, H. D. Ochs, Novel STAT3 mutations, reduced TH17 cell numbers, and variably defective STAT3 phosphorylation in Hyper-IgE syndrome. J. Allergy Clin. Immunol. 122, 181–187 (2008).
10. N. Dagoneau, D. Scheffer, C. Huber, L. I. Al-Gazali, M. D. Rocco, A. Godard, J. Martinovic, A. Raas-Rothschild, S. Sigaudy, S. Unger, S. Nicole, B. Fontaine, J.-L. Taupin, J.-F. Moreau, A. Superti-Furga, M. L. Merrer, J. Bonaventure, A. Munnich, L. Legeai-Mallet, V. Cormier-Daire, Null leukemia inhibitory factor receptor (LIFR) mutations in Stüve-Wiedemann/ Schwartz-Jampel type 2 syndrome. Am. J. Hum. Genet. 74, 298–305 (2004).
11. P. Nieminen, N. V. Morgan, A. L. Fenwick, S. Parmanen, L. Veistinen, M. L. Mikkola, P. J. van der Spek, A. Giraud, L. Judd, S. Arte, L. A. Brueton, S. A. Wall, I. M. J. Mathijssen, E. R. Maher, A. O. M. Wilkie, S. Kreiborg, I. Thesleff, Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth. Am. J. Hum. Genet. 89, 67–81 (2011).
12. T. Schwerd, S. R. F. Twigg, D. Aschenbrenner, S. Manrique, K. A. Miller, I. B. Taylor, M. Capitani, S. J. McGowan, E. Sweeney, A. Weber, L. Chen, P. Bowness, A. Riordan, A. Cant, A. F. Freeman, J. D. Milner, S. M. Holland, N. Frede, M. Müller, D. Schmidt-Arras, B. Grimbacher, S. A. Wall, E. Y. Jones, A. O. M. Wilkie, H. H. Uhlig, A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis. J. Exp. Med. 214, 2547–2562 (2017).
13. + T-cell memory formation and function. J. Allergy Clin. Immunol. 132, 400–411.e9 (2013).
14. C. S. Ma, G. Y. J. Chew, N. Simpson, A. Priyadarshi, M. Wong, B. Grimbacher, D. A. Fulcher, S. G. Tangye, M. C. Cook, Deficiency of TH17 cells in hyper IgE syndrome due to mutations in STAT3. J. Exp. Med. 205, 1551–1557 (2008).
15. C. S. Ma, D. T. Avery, A. Chan, M. Batten, J. Bustamante, S. Boisson-Dupuis, P. D. Arkwright, A. Y. Kreins, D. Averbuch, D. Engelhard, K. Magdorf, S. S. Kilic, Y. Minegishi, S. Nonoyama, M. A. French, S. Choo, J. M. Smart, J. Peake, M. Wong, P. Gray, M. C. Cook, D. A. Fulcher, J.-L. Casanova, E. K. Deenick, S. G. Tangye, Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood 119, 3997–4008 (2012).
16. A. M. Siegel, J. Heimall, A. F. Freeman, A. P. Hsu, E. Brittain, J. M. Brenchley, D. C. Douek, G. H. Fahle, J. I. Cohen, S. M. Holland, J. D. Milner, A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 35, 806–818 (2011).
17. R. P. Wilson, M. L. Ives, G. Rao, A. Lau, K. Payne, M. Kobayashi, P. D. Arkwright, J. Peake, M. Wong, S. Adelstein, J. M. Smart, M. A. French, D. A. Fulcher, C. Picard, J. Bustamante, S. Boisson-Dupuis, P. Gray, P. Stepensky, K. Warnatz, A. F. Freeman, J. Rossjohn, J. McCluskey, S. M. Holland, J.-L. Casanova, G. Uzel, C. S. Ma, S. G. Tangye, E. K. Deenick, STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function. J. Exp. Med. 212, 855–864 (2015).
18. E. K. Deenick, D. T. Avery, A. Chan, L. J. Berglund, M. L. Ives, L. Moens, J. L. Stoddard, J. Bustamante, S. Boisson-Dupuis, M. Tsumura, M. Kobayashi, P. D. Arkwright, D. Averbuch, D. Engelhard, J. Roesler, J. Peake, M. Wong, S. Adelstein, S. Choo, J. M. Smart, M. A. French, D. A. Fulcher, M. C. Cook, C. Picard, A. Durandy, C. Klein, S. M. Holland, G. Uzel, J.-L. Casanova, C. S. Ma, S. G. Tangye, Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells. J. Exp. Med. 210, 2739–2753 (2013).
19. D. Kotlarz, N. Ziętara, G. Uzel, T. Weidemann, C. J. Braun, J. Diestelhorst, P. M. Krawitz, P. N. Robinson, J. Hecht, J. Puchałka, E. M. Gertz, A. A. Schäffer, M. G. Lawrence, L. Kardava, D. Pfeifer, U. Baumann, E.-D. Pfister, E. P. Hanson, A. Schambach, R. Jacobs, H. Kreipe, S. Moir, J. D. Milner, P. Schwille, S. Mundlos, C. Klein, Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome. J. Exp. Med. 210, 433–443 (2013).
20. Y. Minegishi, M. Saito, M. Nagasawa, H. Takada, T. Hara, S. Tsuchiya, K. Agematsu, M. Yamada, N. Kawamura, T. Ariga, I. Tsuge, H. Karasuyama, Molecular explanation for the contradiction between systemic TH17 defect and localized bacterial infection in hyper-IgE syndrome. J. Exp. Med. 206, 1291–1301 (2009).
21. A. Puel, S. Cypowyj, J. Bustamante, J. F. Wright, L. Liu, H. K. Lim, M. Migaud, L. Israel, M. Chrabieh, M. Audry, M. Gumbleton, A. Toulon, C. Bodemer, J. El-Baghdadi, M. Whitters, T. Paradis, J. Brooks, M. Collins, N. M. Wolfman, S. Al-Muhsen, M. Galicchio, L. Abel, C. Picard, J.-L. Casanova, Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332, 65–68 (2011).
22. + T cells into distinct effector subsets. J. Exp. Med. 213, 1589–1608 (2016).
23. M. Giacomelli, N. Tamassia, D. Moratto, P. Bertolini, G. Ricci, C. Bertulli, A. Plebani, M. Cassatella, F. Bazzoni, R. Badolato, SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function. Eur. J. Immunol. 41, 3075–3084 (2011).
24. E.-O. Glocker, D. Kotlarz, C. Klein, N. Shah, B. Grimbacher, IL-10 and IL-10 receptor defects in humans. Ann. N. Y. Acad. Sci. 1246, 102–107 (2011).
25. K. R. Engelhardt, S. McGhee, S. Winkler, A. Sassi, C. Woellner, G. Lopez-Herrera, A. Chen, H. S. Kim, M. G. Lloret, I. Schulze, S. Ehl, J. Thiel, D. Pfeifer, H. Veelken, T. Niehues, K. Siepermann, S. Weinspach, I. Reisli, S. Keles, F. Genel, N. Kutuculer, Y. Camcıoğlu, A. Somer, E. Karakoc-Aydiner, I. Barlan, A. Gennery, A. Metin, A. Degerliyurt, M. C. Pietrogrande, M. Yeganeh, Z. Baz, S. Al-Tamemi, C. Klein, J. M. Puck, S. M. Holland, E. R. B. McCabe, B. Grimbacher, T. A. Chatila, Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J. Allergy Clin. Immunol. 124, 1289–1302.e4 (2009).
26. Q. Zhang, J. C. Davis, I. T. Lamborn, A. F. Freeman, H. Jing, A. J. Favreau, H. F. Matthews, J. Davis, M. L. Turner, G. Uzel, S. M. Holland, H. C. Su, Combined immunodeficiency associated with DOCK8 mutations. N. Engl. J. Med. 361, 2046–2055 (2009).
27. Q. Zhang, C. G. Dove, J. L. Hor, H. M. Murdock, D. M. Strauss-Albee, J. A. Garcia, J. N. Mandl, R. A. Grodick, H. Jing, D. B. Chandler-Brown, T. E. Lenardo, G. Crawford, H. F. Matthews, A. F. Freeman, R. J. Cornall, R. N. Germain, S. N. Mueller, H. C. Su, DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J. Exp. Med. 211, 2549–2566 (2014).
28. Q. Zhang, H. Jing, H. C. Su, Recent advances in DOCK8 immunodeficiency syndrome. J. Clin. Immunol. 36, 441–449 (2016).
29. A. Sassi, S. Lazaroski, G. Wu, S. M. Haslam, M. Fliegauf, F. Mellouli, T. Patiroglu, E. Unal, M. A. Ozdemir, Z. Jouhadi, K. Khadir, L. Ben-Khemis, M. Ben-Ali, I. Ben-Mustapha, L. Borchani, D. Pfeifer, T. Jakob, M. Khemiri, A. C. Asplund, M. O. Gustafsson, K. E. Lundin, E. Falk-Sörqvist, L. N. Moens, H. E. Gungor, K. R. Engelhardt, M. Dziadzio, H. Stauss, B. Fleckenstein, R. Meier, K. Prayitno, A. Maul-Pavicic, S. Schaffer, M. Rakhmanov, P. Henneke, H. Kraus, H. Eibel, U. Kölsch, S. Nadifi, M. Nilsson, M. Bejaoui, A. A. Schäffer, C. I. E. Smith, A. Dell, M.-R. Barbouche, B. Grimbacher, Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J. Allergy Clin. Immunol. 133, 1410–1419.e13 (2014).
30. Y. Zhang, X. Yu, M. Ichikawa, J. J. Lyons, S. Datta, I. T. Lamborn, H. Jing, E. S. Kim, M. Biancalana, L. A. Wolfe, T. DiMaggio, H. F. Matthews, S. M. Kranick, K. D. Stone, S. M. Holland, D. S. Reich, J. D. Hughes, H. Mehmet, J. McElwee, A. F. Freeman, H. H. Freeze, H. C. Su, J. D. Milner, Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J. Allergy Clin. Immunol. 133, 1400–1409.e5 (2014).
31. A. Belkadi, V. Pedergnana, A. Cobat, Y. Itan, Q. B. Vincent, A. Abhyankar, L. Shang, J. E. Baghdadi, A. Bousfiha; Exome/Array Consortium, A. Alcais, B. Boisson, J.-L. Casanova, L. Abel, W. Al-Herz, C. Arikan, P. Arkwright, C. Aydogmus, O. Bernard, L. Blancas-Galicia, S. Boisson-Dupuis, D. Bonnet, O. B. Stambouli, L. Boussofara, J. Boutros, J. Bustamante, M. Ciancanelli, T. Cole, A. Condino-Neto, M. Desai, C. Fieschi, J. L. Franco, P. Ichai, E. Jouanguy, M. Keser-Emiroglu, S. S. Kilic, S. A. Mahdaviani, N. Mahlhoui, D. Mansouri, N. Parvaneh, C. Picard, A. Puel, D. Raoult, N. Rezaei, O. Sanal, S. S. Ramon, F. Vandenesch, G. Vogt, S.-Y. Zhang, Whole-exome sequencing to analyze population structure, parental inbreeding, and familial linkage. Proc. Natl. Acad. Sci. U.S.A. 113, 6713–6718 (2016).
32. M. Kircher, D. M. Witten, P. Jain, B. J. O’Roak, G. M. Cooper, J. Shendure, A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310–315 (2014).
33. Y. Itan, L. Shang, B. Boisson, M. J. Ciancanelli, J. G. Markle, R. Martinez-Barricarte, E. Scott, I. Shah, P. D. Stenson, J. Gleeson, D. N. Cooper, L. Quintana-Murci, S.-Y. Zhang, L. Abel, J.-L. Casanova, The mutation significance cutoff: Gene-level thresholds for variant predictions. Nat. Methods 13, 109–110 (2016).
34. M. Cokol, R. Nair, B. Rost, Finding nuclear localization signals. EMBO Rep. 1, 411–415 (2000).
35. T. Goldberg, T. Hamp, B. Rost, LocTree2 predicts localization for all domains of life. Bioinformatics 28, i458–i465 (2012).
36. M. Ichiba, K. Nakajima, Y. Yamanaka, N. Kiuchi, T. Hirano, Autoregulation of the Stat3 gene through cooperation with a cAMP-responsive element-binding protein. J. Biol. Chem. 273, 6132–6138 (1998).
37. M. Narimatsu, H. Maeda, S. Itoh, T. Atsumi, T. Ohtani, K. Nishida, M. Itoh, D. Kamimura, S.-J. Park, K. Mizuno, J.-I. Miyazaki, M. Hibi, K. Ishihara, K. Nakajima, T. Hirano, Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells. Mol. Cell. Biol. 21, 6615–6625 (2001).
38. M.-J. Kwon, J. Ma, Y. Ding, R. Wang, Z. Sun, Protein kinase C- promotes TH17 differentiation via upregulation of Stat3. J. Immunol. 188, 5887–5897 (2012).
39. L. Liu, S. Okada, X.-F. Kong, A. Y. Kreins, S. Cypowyj, A. Abhyankar, J. Toubiana, Y. Itan, M. Audry, P. Nitschke, C. Masson, B. Toth, J. Flatot, M. Migaud, M. Chrabieh, T. Kochetkov, A. Bolze, A. Borghesi, A. Toulon, J. Hiller, S. Eyerich, K. Eyerich, V. Gulácsy, L. Chernyshova, V. Chernyshov, A. Bondarenko, R. M. C. Grimaldo, L. Blancas-Galicia, I. M. M. Beas, J. Roesler, K. Magdorf, D. Engelhard, C. Thumerelle, P.-R. Burgel, M. Hoernes, B. Drexel, R. Seger, T. Kusuma, A. F. Jansson, J. Sawalle-Belohradsky, B. Belohradsky, E. Jouanguy, J. Bustamante, M. Bué, N. Karin, G. Wildbaum, C. Bodemer, O. Lortholary, A. Fischer, S. Blanche, S. Al-Muhsen, J. Reichenbach, M. Kobayashi, F. E. Rosales, C. T. Lozano, S. S. Kilic, M. Oleastro, A. Etzioni, C. Traidl-Hoffmann, E. D. Renner, L. Abel, C. Picard, L. Maródi, S. Boisson-Dupuis, A. Puel, J.-L. Casanova, Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J. Exp. Med. 208, 1635–1648 (2011).
40. F. L. van de Veerdonk, T. S. Plantinga, A. Hoischen, S. P. Smeekens, L. A. B. Joosten, C. Gilissen, P. Arts, D. C. Rosentul, A. J. Carmichael, C. A. A. Smits-van der Graaf, B. J. Kullberg, J. W. M. van der Meer, D. Lilic, J. A. Veltman, M. G. Netea, STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N. Engl. J. Med. 365, 54–61 (2011).
41. S. Okada, J. G. Markle, E. K. Deenick, F. Mele, D. Averbuch, M. Lagos, M. Alzahrani, S. Al-Muhsen, R. Halwani, C. S. Ma, N. Wong, C. Soudais, L. A. Henderson, H. Marzouqa, J. Shamma, M. Gonzalez, R. Martinez-Barricarte, C. Okada, D. T. Avery, D. Latorre, C. Deswarte, F. Jabot-Hanin, E. Torrado, J. Fountain, A. Belkadi, Y. Itan, B. Boisson, M. Migaud, C. S. L. Arlehamn, A. Sette, S. Breton, J. McCluskey, J. Rossjohn, J.-P. de Villartay, D. Moshous, S. Hambleton, S. Latour, P. D. Arkwright, C. Picard, O. Lantz, D. Engelhard, M. Kobayashi, L. Abel, A. M. Cooper, L. D. Notarangelo, S. Boisson-Dupuis, A. Puel, F. Sallusto, J. Bustamante, S. G. Tangye, J.-L. Casanova, Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349, 606–613 (2015).
42. J. Toubiana, S. Okada, J. Hiller, M. Oleastro, M. L. Gomez, J. C. A. Becerra, M. Ouachée-Chardin, F. Fouyssac, K. M. Girisha, A. Etzioni, J. V. Montfrans, Y. Camcioglu, L. A. Kerns, B. Belohradsky, S. Blanche, A. Bousfiha, C. Rodriguez-Gallego, I. Meyts, K. Kisand, J. Reichenbach, E. D. Renner, S. Rosenzweig, B. Grimbacher, F. L. van de Veerdonk, C. Traidl-Hoffmann, C. Picard, L. Marodi, T. Morio, M. Kobayashi, D. Lilic, J. D. Milner, S. Holland, J.-L. Casanova, A. Puel; International STAT1 Gain-of-Function Study Group, Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 127, 3154–3164 (2016).
43. R. Lévy, S. Okada, V. Béziat, K. Moriya, C. Liu, L. Y. A. Chai, M. Migaud, F. Hauck, A. A. Ali, C. Cyrus, C. Vatte, T. Patiroglu, E. Unal, M. Ferneiny, N. Hyakuna, S. Nepesov, M. Oleastro, A. Ikinciogullari, F. Dogu, T. Asano, O. Ohara, L. Yun, E. D. Mina, D. Bronnimann, Y. Itan, F. Gothe, J. Bustamante, S. Boisson-Dupuis, N. Tahuil, C. Aytekin, A. Salhi, S. A. Muhsen, M. Kobayashi, J. Toubiana, L. Abel, X. Li, Y. Camcioglu, F. Celmeli, C. Klein, S. A. AlKhater, J.-L. Casanova, A. Puel, Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. Proc. Natl. Acad. Sci. U.S.A. 113, E8277–E8285 (2016).
44. Y. Ling, S. Cypowyj, C. Aytekin, M. Galicchio, Y. Camcioglu, S. Nepesov, A. Ikinciogullari, F. Dogu, A. Belkadi, R. Levy, M. Migaud, B. Boisson, A. Bolze, Y. Itan, N. Goudin, J. Cottineau, C. Picard, L. Abel, J. Bustamante, J.-L. Casanova, A. Puel, Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J. Exp. Med. 212, 619–631 (2015).
45. B. Boisson, C. Wang, V. Pedergnana, L. Wu, S. Cypowyj, M. Rybojad, A. Belkadi, C. Picard, L. Abel, C. Fieschi, A. Puel, X. Li, J.-L. Casanova, An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity 39, 676–686 (2013).
46. L. de Beaucoudrey, A. Puel, O. Filipe-Santos, A. Cobat, P. Ghandil, M. Chrabieh, J. Feinberg, H. von Bernuth, A. Samarina, L. Jannière, C. Fieschi, J.-L. Stéphan, C. Boileau, S. Lyonnet, G. Jondeau, V. Cormier-Daire, M. Le Merrer, C. Hoarau, Y. Lebranchu, O. Lortholary, M.-O. Chandesris, F. Tron, E. Gambineri, L. Bianchi, C. Rodriguez-Gallego, S. E. Zitnik, J. Vasconcelos, M. Guedes, A. B. Vitor, L. Marodi, H. Chapel, B. Reid, C. Roifman, D. Nadal, J. Reichenbach, I. Caragol, B.-Z. Garty, F. Dogu, Y. Camcioglu, S. Gülle, O. Sanal, A. Fischer, L. Abel, B. Stockinger, C. Picard, J.-L. Casanova, Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells. J. Exp. Med. 205, 1543–1550 (2008).
47. J. D. Milner, J. M. Brenchley, A. Laurence, A. F. Freeman, B. J. Hill, K. M. Elias, Y. Kanno, C. Spalding, H. Z. Elloumi, M. L. Paulson, J. Davis, A. Hsu, A. I. Asher, J. O’Shea, S. M. Holland, W. E. Paul, D. C. Douek, Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452, 773–776 (2008).
48. E. V. Acosta-Rodriguez, L. Rivino, J. Geginat, D. Jarrossay, M. Gattorno, A. Lanzavecchia, F. Sallusto, G. Napolitani, Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells. Nat. Immunol. 8, 639–646 (2007).
49. C. S. Ma, N. Wong, G. Rao, D. T. Avery, J. Torpy, T. Hambridge, J. Bustamante, S. Okada, J. L. Stoddard, E. K. Deenick, S. J. Pelham, K. Payne, S. Boisson-Dupuis, A. Puel, M. Kobayashi, P. D. Arkwright, S. S. Kilic, J. El Baghdadi, S. Nonoyama, Y. Minegishi, S. A. Mahdaviani, D. Mansouri, A. Bousfiha, A. K. Blincoe, M. A. French, P. Hsu, D. E. Campbell, M. O. Stormon, M. Wong, S. Adelstein, J. M. Smart, D. A. Fulcher, M. C. Cook, T. G. Phan, P. Stepensky, K. Boztug, A. Kansu, A. İkincioğullari, U. Baumann, R. Beier, T. Roscioli, J. B. Ziegler, P. Gray, C. Picard, B. Grimbacher, K. Warnatz, S. M. Holland, J.-L. Casanova, G. Uzel, S. G. Tangye, Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies. J. Allergy Clin. Immunol. 136, 993–1006.e1 (2015).
50. K. Bønnelykke, R. Sparks, J. Waage, J. D. Milner, Genetics of allergy and allergic sensitization: Common variants, rare mutations. Curr. Opin. Immunol. 36, 115–126 (2015).
51. C. A. Ma, J. R. Stinson, Y. Zhang, J. K. Abbott, M. A. Weinreich, P. J. Hauk, P. R. Reynolds, J. J. Lyons, C. G. Nelson, E. Ruffo, B. Dorjbal, S. Glauzy, N. Yamakawa, S. Arjunaraja, K. Voss, J. Stoddard, J. Niemela, Y. Zhang, S. D. Rosenzweig, J. J. McElwee, T. DiMaggio, H. F. Matthews, N. Jones, K. D. Stone, A. Palma, M. Oleastro, E. Prieto, A. R. Bernasconi, G. Dubra, S. Danielian, J. Zaiat, M. A. Marti, B. Kim, M. A. Cooper, N. Romberg, E. Meffre, E. W. Gelfand, A. L. Snow, J. D. Milner, Germline hypomorphic CARD11 mutations in severe atopic disease. Nat. Genet. 49, 1192–1201 (2017).
52. + T cells initiate atopic dermatitis lesions. J. Immunol. 178, 5571–5577 (2007).
53. + T cells are recruited early to allergen exposure sites in atopy patch test reactions in human atopic dermatitis. J. Allergy Clin. Immunol. 127, 1064–1067 (2011).
54. H. F. Rosenberg, K. D. Dyer, P. S. Foster, Eosinophils: Changing perspectives in health and disease. Nat. Rev. Immunol. 13, 9–22 (2013).
55. M. H. Kaplan, M. M. Hufford, M. R. Olson, The development and in vivo function of T helper 9 cells. Nat. Rev. Immunol. 15, 295–307 (2015).
56. C. E. Bocchini, K. Nahmod, P. Katsonis, S. Kim, M. M. Kasembeli, A. Freeman, O. Lichtarge, G. Makedonas, D. J. Tweardy, Protein stabilization improves STAT3 function in autosomal dominant hyper-IgE syndrome. Blood 128, 3061–3072 (2016).
57. S. J. Pelham, H. C. Lenthall, E. K. Deenick, S. G. Tangye, Elucidating the effects of disease-causing mutations on STAT3 function in autosomal-dominant hyper-IgE syndrome. J. Allergy Clin. Immunol. 138, 1210–1213.e5 (2016).
58. J. Wienke, W. Janssen, R. Scholman, H. Spits, M. van Gijn, M. Boes, J. van Montfrans, N. Moes, S. de Roock, A novel human STAT3 mutation presents with autoimmunity involving TH17 hyperactivation. Oncotarget 6, 20037–20042 (2015).
59. X. O. Yang, A. D. Panopoulos, R. Nurieva, S. H. Chang, D. Wang, S. S. Watowich, C. Dong, STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem. 282, 9358–9363 (2007).
60. S. Boisson-Dupuis, X.-F. Kong, S. Okada, S. Cypowyj, A. Puel, L. Abel, J.-L. Casanova, Inborn errors of human STAT1: Allelic heterogeneity governs the diversity of immunological and infectious phenotypes. Curr. Opin. Immunol. 24, 364–378 (2012).
61. J.-L. Casanova, L. Abel, L. Quintana-Murci, Immunology taught by human genetics. Cold Spring Harb. Symp. Quant. Biol. 78, 157–172 (2013).
62. L. D. Notarangelo, T. A. Fleisher, Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders. J. Allergy Clin. Immunol. 139, 715–723 (2017).
63. Y. Zhang, H. C. Su, M. J. Lenardo, Genomics is rapidly advancing precision medicine for immunological disorders. Nat. Immunol. 16, 1001–1004 (2015).
64. J.-L. Casanova, L. Abel, Human genetics of infectious diseases: Unique insights into immunological redundancy. Semin. Immunol. 36, 1–12 (2018).
65. W. J. Leonard, J. J. O’Shea, JAKS AND STATS: Biological Implications. Annu. Rev. Immunol. 16, 293–322 (1998).
66. D. E. Levy, J. E. Darnell Jr., STATs: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3, 651–662 (2002).
67. J. Yang, X. Liao, M. K. Agarwal, L. Barnes, P. E. Auron, G. R. Stark, Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFB. Genes Dev. 21, 1396–1408 (2007).
68. A. V. Villarino, Y. Kanno, J. J. O’Shea, Mechanisms and consequences of Jak–STAT signaling in the immune system. Nat. Immunol. 18, 374–384 (2017).
69. S. E. Flanagan, E. Haapaniemi, M. A. Russell, R. Caswell, H. L. Allen, E. De Franco, T. J. McDonald, H. Rajala, A. Ramelius, J. Barton, K. Heiskanen, T. Heiskanen-Kosma, M. Kajosaari, N. P. Murphy, T. Milenkovic, M. Seppänen, Å. Lernmark, S. Mustjoki, T. Otonkoski, J. Kere, N. G. Morgan, S. Ellard, A. T. Hattersley, Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat. Genet. 46, 812–814 (2014).
70. E. M. Haapaniemi, M. Kaustio, H. L. M. Rajala, A. J. van Adrichem, L. Kainulainen, V. Glumoff, R. Doffinger, H. Kuusanmäki, T. Heiskanen-Kosma, L. Trotta, S. Chiang, P. Kulmala, S. Eldfors, R. Katainen, S. Siitonen, M.-L. Karjalainen-Lindsberg, P. E. Kovanen, T. Otonkoski, K. Porkka, K. Heiskanen, A. Hänninen, Y. T. Bryceson, R. Uusitalo-Seppälä, J. Saarela, M. Seppänen, S. Mustjoki, J. Kere, Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood 125, 639–648 (2015).
71. J. D. Milner, T. P. Vogel, L. Forbes, C. A. Ma, A. Stray-Pedersen, J. E. Niemela, J. J. Lyons, K. R. Engelhardt, Y. Zhang, N. Topcagic, E. D. O. Roberson, H. Matthews, J. W. Verbsky, T. Dasu, A. Vargas-Hernandez, N. Varghese, K. L. McClain, L. B. Karam, K. Nahmod, G. Makedonas, E. M. Mace, H. S. Sorte, G. Perminow, V. K. Rao, M. P. O’Connell, S. Price, H. C. Su, M. Butrick, J. McElwee, J. D. Hughes, J. Willet, D. Swan, Y. Xu, M. Santibanez-Koref, V. Slowik, D. L. Dinwiddie, C. E. Ciaccio, C. J. Saunders, S. Septer, S. F. Kingsmore, A. J. White, A. J. Cant, S. Hambleton, M. A. Cooper, Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood 125, 591–599 (2015).
72. B. Grimbacher, A. A. Schäffer, S. M. Holland, J. Davis, J. I. Gallin, H. L. Malech, T. P. Atkinson, B. H. Belohradsky, R. H. Buckley, F. Cossu, T. Español, B.-Z. Garty, N. Matamoros, L. A. Myers, R. P. Nelson, H. D. Ochs, E. D. Renner, N. Wellinghausen, J. M. Puck, Genetic linkage of hyper-IgE syndrome to chromosome 4. Am. J. Hum. Genet. 65, 735–744 (1999).
73. H. Li, R. Durbin, Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 26, 589–595 (2010).
74. A. McKenna, M. Hanna, E. Banks, A. Sivachenko, K. Cibulskis, A. Kernytsky, K. Garimella, D. Altshuler, S. Gabriel, M. Daly, M. A. DePristo, The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
75. H. Li, B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, R. Durbin; 1000 Genome Project Data Processing Subgroup, The sequence alignment/ map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
76. I. A. Adzhubei, S. Schmidt, L. Peshkin, V. E. Ramensky, A. Gerasimova, P. Bork, A. S. Kondrashov, S. R. Sunyaev, A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).
77. P. C. Ng, S. Henikoff, Predicting deleterious amino acid substitutions. Genome Res. 11, 863–874 (2001).
78. B. Fleckenstein, A. Ensser, Herpesvirus saimiri transformation of human T lymphocytes, in Current Protocols in Immunology (John Wiley & Sons Inc., 2001).
79. Y. Zhang, T. Liu, C. A. Meyer, J. Eeckhoute, D. S. Johnson, B. E. Bernstein, C. Nusbaum, R. M. Myers, M. Brown, W. Li, X. S. Liu, Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
80. D. J. McCarthy, Y. Chen, G. K. Smyth, Differential expression analysis of multifactor RNA-seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288–4297 (2012).
81. V. Béziat, B. Descours, C. Parizot, P. Debré, V. Vieillard, NK cell terminal differentiation: Correlated stepwise decrease of NKG2A and acquisition of KIRs. PLOS ONE 5, e11966 (2010).
82. dim NK-cell differentiation uncoupled from NK-cell education. Blood 116, 3853–3864 (2010).
83. A. I. Lim, Y. Li, S. Lopez-Lastra, R. Stadhouders, F. Paul, A. Casrouge, N. Serafini, A. Puel, J. Bustamante, L. Surace, G. Masse-Ranson, E. David, H. Strick-Marchand, L. Le Bourhis, R. Cocchi, D. Topazio, P. Graziano, L. A. Muscarella, L. Rogge, X. Norel, J.-M. Sallenave, M. Allez, T. Graf, R. W. Hendriks, J.-L. Casanova, I. Amit, H. Yssel, J. P. Di Santo, Systemic human ILC precursors provide a substrate for tissue ILC differentiation. Cell 168, 1086–1100.e10 (2017).
84. R. A. de Paus, M. A. Geilenkirchen, S. van Riet, J. T. van Dissel, E. van de Vosse, Differential expression and function of human IL-12R2 polymorphic variants. Mol. Immunol. 56, 380–389 (2013).