IL-7 promotes TH1 development and serum IL-7 predicts clinical response to interferon-β in multiple sclerosis

Science Translational Medicine

Volumn 3, Issue 93, 2011, Pages

  Lee, Li Fen ^a   Axtell, Robert ^b   Tu, Guang Huan ^a   Logronio, Kathryn ^a   Dilley, Jeanette ^a   Yu, Jessica ^a   Rickert, Mathias ^a   Han, Bora ^a   Evering, Winston ^a   Walker, Michael G ^c   Shi, Jing ^c   De Jong, Brigit A ^d   Killestein, Joep ^e   Polman, Chris H ^e   Steinman, Lawrence ^b   Lin, John C ^a  

^a PFIZER INC   (United States)

^b STANFORD UNIVERSITY   (United States)

^c Walker Bioscience   (United States)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 17F; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR ALPHA ANTIBODY; RECEPTOR ANTIBODY; UNCLASSIFIED DRUG; ANTIBODY; INTERLEUKIN 7 RECEPTOR; INTERLEUKIN 7 RECEPTOR, ALPHA CHAIN; INTERLEUKIN-7 RECEPTOR, ALPHA CHAIN;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CELL MATURATION; CENTRAL NERVOUS SYSTEM; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; CYTOKINE RESPONSE; DRUG RESPONSE; FEMALE; HUMAN; HUMAN CELL; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTIC INFILTRATION; MEMORY T LYMPHOCYTE; MOUSE; MULTIPLE SCLEROSIS; NATURAL KILLER CELL; NONHUMAN; ONSET AGE; PARALYSIS; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; PROTEIN TARGETING; RAT; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; ANIMAL; ANTIBODY SPECIFICITY; BLOOD; CELL DIFFERENTIATION; CYTOLOGY; DRUG ANTAGONISM; DRUG EFFECT; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; PATHOLOGY; TREATMENT OUTCOME;

ANIMALS; ANTIBODIES; ANTIBODY SPECIFICITY; CELL DIFFERENTIATION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; IMMUNOLOGIC MEMORY; INTERFERON-BETA; INTERLEUKIN-7; MICE; MULTIPLE SCLEROSIS; RECEPTORS, INTERLEUKIN-7; TH1 CELLS; TREATMENT OUTCOME;

EID: 79960787295     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002400     Document Type: Article

References (39)

1. H. F. McFarland, R. Martin, Multiple sclerosis: A complicated picture of autoimmunity. Nat. Immunol. 8, 913-919 (2007).
2. M. Sospedra, R. Martin, Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683-747 (2005).
3. C. Confavreux, S. Vukusic, P. Adeleine, Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process. Brain 126, 770-782 (2003).
4. F. Lundmark, K.Duvefelt, E. Iacobaeus, I. Kockum, E. Wallström, M. Khademi, A. Oturai, L. P. Ryder, J. Saarela, H. F. Harbo, E. G. Celius, H. Salter, T. Olsson, J. Hillert, Variation in interleukin 7 receptor a chain (IL7R) influences risk of multiple sclerosis. Nat. Genet. 39, 1108-1113 (2007).
5. International Multiple Sclerosis Genetics Consortium, D. A. Hafler, A. Compston, S. Sawcer, E. S. Lander, M. J. Daly, P. L. De Jager, P. I. de Bakker, S. B. Gabriel, D. B. Mirel, A. J. Ivinson, M. A. Pericak-Vance, S. G. Gregory, J. D. Rioux, J. L. McCauley, J. L. Haines, L. F. Barcellos, B. Cree, J. R. Oksenberg, S. L. Hauser, Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med. 357, 851-862 (2007).
6. S. G. Gregory, S. Schmidt, P. Seth, J. R. Oksenberg, J. Hart, A. Prokop, S. J. Caillier, M. Ban, A. Goris, L. F. Barcellos, R. Lincoln, J. L. McCauley, S. J. Sawcer, D. A. Compston, B. Dubois, S. L. Hauser, M. A. Garcia-Blanco, M. A. Pericak-Vance, J. L. Haines; Multiple Sclerosis Genetics Group, Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39, 1083-1091 (2007).
7. W. J. Leonard, E. W. Shores, P. E. Love, Role of the common cytokine receptor γ chain in cytokine signaling and lymphoid development. Immunol. Rev. 148, 97-114 (1995).
8. T. Habib, S. Senadheera, K. Weinberg, K. Kaushansky, The common γ chain (γc) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry 41, 8725-8731 (2002).
9. H. Asao, C. Okuyama, S. Kumaki, N. Ishii, S. Tsuchiya, D. Foster, K. Sugamura, Cutting edge: The common γ-chain is an indispensable subunit of the IL-21 receptor complex. J. Immunol. 167, 1-5 (2001).
10. M. J. Palmer, V. S. Mahajan, L. C. Trajman, D. J. Irvine, D. A. Lauffenburger, J. Chen, Interleukin-7 receptor signaling network: An integrated systems perspective. Cell. Mol. Immunol. 5, 79-89 (2008).
11. Q. Jiang, W. Q. Li, F. B. Aiello, R. Mazzucchelli, B. Asefa, A. R. Khaled, S. K. Durum, Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 16, 513-533 (2005).
12. L. S. Park, U. Martin, K. Garka, B. Gliniak, J. P. Di Santo, W. Muller, D. A. Largaespada, N. G. Copeland, N. A. Jenkins, A. G. Farr, S. F. Ziegler, P. J. Morrissey, R. Paxton, J. E. Sims, Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med. 192, 659-670 (2000).
13. W. J. Leonard, TSLP: Finally in the limelight. Nat. Immunol. 3, 605-607 (2002).
14. U. von Freeden-Jeffry, P. Vieira, L. A. Lucian, T. McNeil, S. E. Burdach, R. Murray, Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181, 1519-1526 (1995).
15. B. Seddon, P. Tomlinson, R. Zamoyska, Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat. Immunol. 4, 680-686 (2003).
16. + severe combined immunodeficiency. Nat. Genet. 20, 394-397 (1998).
17. J. J. Peschon, P. J. Morrissey, K. H. Grabstein, F. J. Ramsdell, E. Maraskovsky, B. C. Gliniak, L. S. Park, S. F. Ziegler, D. E. Williams, C. B. Ware, J. D. Meyer, B. L. Davison, Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180, 1955-1960 (1994).
18. T. J. Fry, C. L. Mackall, The many faces of IL-7: From lymphopoiesis to peripheral T cell maintenance. J. Immunol. 174, 6571-6576 (2005).
19. B. Bielekova, P. A. Muraro, L. Golestaneh, J. Pascal, H. F. McFarland, R. Martin, Preferential expansion of autoreactive T lymphocytes from the memory T-cell pool by IL-7. J. Neuroimmunol. 100, 115-123 (1999).
20. S. G. Gregory, S. Schmidt, P. Seth, J. R. Oksenberg, J. Hart, A. Prokop, S. J. Caillier, M. Ban, A. Goris, L. F. Barcellos, R. Lincoln, J. L. McCauley, S. J. Sawcer, D. A. Compston, B. Dubois, S. L. Hauser, M. A. Garcia-Blanco, M. A. Pericak-Vance, J. L. Haines; Multiple Sclerosis Genetics Group, Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 39, 1083-1091 (2007).
21. R. C. Axtell, B. A. de Jong, K. Boniface, L. F. van der Voort, R. Bhat, P. De Sarno, R. Naves, M. Han, F. Zhong, J. G. Castellanos, R. Mair, A. Christakos, I. Kolkowitz, L. Katz, J. Killestein, C. H. Polman, R. de Waal Malefyt, L. Steinman, C. Raman, T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nat. Med. 16, 406-412 (2010).
22. T. Sing, O. Sander, N. Beerenwinkel, T. Lengauer, ROCR: Visualizing classifier performance in R. Bioinformatics 21, 3940-3941 (2005).
23. X. Liu, S. Leung, C. Wang, Z. Tan, J. Wang, T. B. Guo, L. Fang, Y. Zhao, B. Wan, X. Qin, L. Lu, R. Li, H. Pan, M. Song, A. Liu, J. Hong, H. Lu, J. Z. Zhang, Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease. Nat. Med. 16, 191-197 (2010).
24. + cells. J. Exp. Med. 195, 1523-1532 (2002).
25. J. T. Tan, E. Dudl, E. LeRoy, R. Murray, J. Sprent, K. I. Weinberg, C. D. Surh, IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc. Natl. Acad. Sci. U.S.A. 98, 8732-8737 (2001).
26. C. D. Surh, J. Sprent, Homeostasis of naive and memory T cells. Immunity 29, 848-862 (2008).
27. C. C. Walline, S. Kanakasabai, J. J. Bright, IL-7Rα confers susceptibility to experimental autoimmune encephalomyelitis. Genes Immun. 12, 1-14 (2011).
28. S. A. Hartgring, C. R. Willis, D. Alcorn, L. J. Nelson, J. W. Bijlsma, F. P. Lafeber, J. A. van Roon, Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators. Arthritis Rheum. 62, 2716-2725 (2010).
29. H-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nat. Immunol. 9, 641-649 (2008).
30. I. I. Ivanov, K. Atarashi, N. Manel, E. L. Brodie, T. Shima, U. Karaoz, D. Wei, K. C. Goldfarb, C. A. Santee, S. V. Lynch, T. Tanoue, A. Imaoka, K. Itoh, K. Takeda, Y. Umesaki, K. Honda, D. R. Littman, Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485-498 (2009).
31. I. I. Ivanov, L. Frutos Rde, N. Manel, K. Yoshinaga, D. B. Rifkin, R. B. Sartor, B. B. Finlay, D. R. Littman, Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337-349 (2008).
32. I. I. Ivanov, D. R. Littman, Segmented filamentous bacteria take the stage. Mucosal Immunol. 3, 209-212 (2010).
33. I. I. Ivanov, D. R. Littman, Modulation of immune homeostasis by commensal bacteria. Curr. Opin. Microbiol. 14, 106-114 (2011).
34. H17 and regulatory T cells. Nature 441, 235-238 (2006).
35. E. Hoe, F. McKay, S. Schibeci, R. Heard, G. Stewart, D. Booth, Interleukin 7 receptor α chain haplotypes vary in their influence on multiple sclerosis susceptibility and response to interferon β. J. Interferon Cytokine Res. 30, 291-298 (2010).
36. M. T. Falta, A. P. Fontenot, E. F. Rosloniec, F. Crawford, C. L. Roark, J. Bill, P. Marrack, J. Kappler, B. L. Kotzin, Class II major histocompatibility complex-peptide tetramer staining in relation to functional avidity and T cell receptor diversity in the mouse CD4+ T cell response to a rheumatoid arthritis-associated antigen. Arthritis Rheum. 52, 1885-1896 (2005).
37. P. O. Krutzik, M. B. Hale, G. P. Nolan, Characterization of the murine immunological signaling network with phosphospecific flow cytometry. J. Immunol. 175, 2366-2373 (2005).
38. P. O. Krutzik, M. R. Clutter, G. P. Nolan, Coordinate analysis of murine immune cell surface markers and intracellular phosphoproteins by flow cytometry. J. Immunol. 175, 2357-2365 (2005).
39. Acknowledgments: We thank M. Gilbert for flow cytometry, M. Chin and A. Rajpal for discussing IL-7 expression and purification approaches, D. Malashock and Y. Abdiche for biosensor assay, S. LaPorte for general discussion on cytokine biology, G. Vergara and T. Radcliff for vivariumsupport, and A. Gholston for help with figures. Funding: This study was funded in part by NIH grants R01NS 55997 (to L.S.) and 1K99NS075099-01 (to R.A.) and a National Multiple Sclerosis Society fellowship FG 1817-A-1 (to R.A.). Author contributions: L.F.-L. and R.A. designed and performed the research, analyzed the data, and wrote the paper; G.H.T. performed the research and analyzed the data; K.L. performed the research; J.D., J.Y., and M.R. contributed vital new reagents; B.H. and W.E. performed the histopathology study and evaluated the slides; M.G.W. and J.S. performed statistical analysis of patient samples; B.A.d.J., J.K., and C.H.P. collected all patient samples; L.S. and J.C.L. designed the research, analyzed the data, and wrote the paper. Competing interests: L.F.-L., G.H.T., K.L., J.D., J.Y., M.R., B.H., W.E., and J.C.L. are full-time employees of Pfizer Inc. Pfizer Inc. filed a patent application, with L.F.-L., J.C.L., and W. Zhai as co-inventors: U.S. Application Serial No. 13/033,491, entitled "Antagonist Anti-IL-7 Receptor Antibodies and Methods." Neither R.A. nor L.S. has consulting relationships with Pfizer Inc. or its Rinat unit. The work at Stanford was not sponsored by Rinat or Pfizer Inc. L.S. has a consulting relationship with GlaxoSmithKline. Stanford University has filed a patent application, with R.A. and L.S. as co-inventors: U.S. Application Serial No. 13/026,181 for "Markers for Determination of Patient Responsiveness." The other authors declare that they have no competing interests.