Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 33, 2016, Pages 9321-9326

  Comte, Denis ^a,b   Karampetsou, Maria P ^a   Kis Toth, Katalin ^a   Yoshida, Nobuya ^a   Bradley, Sean J ^a   Mizui, Masayuki ^a,c   Kono, Michihito ^a   Solomon, Julie R ^a   Kyttaris, Vasileios C ^a   Tsokos, George C ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^c OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Autoimmunity; IL 2; SLAMF3; SLE; Treg

Indexed keywords

CD28 ANTIGEN; CD4 ANTIGEN; GLYCOPROTEIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 2 RECEPTOR GAMMA; MESSENGER RNA; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE FAMILY 3 GLYCOPROTEIN; SMAD3 PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; IL2RA PROTEIN, HUMAN; LY9 PROTEIN, HUMAN; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE;

ARTICLE; BINDING SITE; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CELL SURFACE; CLINICAL ARTICLE; CONTROLLED STUDY; GENETIC TRANSCRIPTION; HUMAN; POLARIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY T LYMPHOCYTE; SENSITIVITY ANALYSIS; SLEDAI; SYSTEMIC LUPUS ERYTHEMATOSUS; UPREGULATION; ADULT; AGED; BIOSYNTHESIS; CELL POLARITY; DRUG EFFECTS; FEMALE; GENETICS; IMMUNOLOGY; MALE; MIDDLE AGED; PHYSIOLOGY;

ADULT; AGED; CD4-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; CELL POLARITY; FEMALE; HUMANS; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MIDDLE AGED; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE FAMILY; T-LYMPHOCYTES, REGULATORY;

EID: 84982105560     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1605081113     Document Type: Article

References (45)

1. Romero X, et al. (2005) CD229 (Ly9) lymphocyte cell surface receptor interacts homophilically through its N-terminal domain and relocalizes to the immunological synapse. J Immunol 174 (11):7033-7042.
2. Cannons JL, Tangye SG, Schwartzberg PL (2011) SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol 29:665-705.
3. Romero X, Sintes J, Engel P (2014) Role of SLAM family receptors and specific adapter SAP in innate-like lymphocytes. Crit Rev Immunol 34 (4):263-299.
4. Tsokos GC (2011) Systemic lupus erythematosus. N Engl J Med 365 (22):2110-2121.
5. Deng Y, Tsao BP (2010) Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat Rev Rheumatol 6 (12):683-692.
6. Wandstrat AE, et al. (2004) Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Immunity 21 (6):769-780.
7. Cunninghame Graham DS, et al.; CaNIOS GenES Investigators (2008) Association of LY9 in UK and Canadian SLE families. Genes Immun 9 (2):93-102.
8. Margraf S, Garner LI, Wilson TJ, Brown MH (2015) A polymorphism in a phosphotyrosine signalling motif of CD229 (Ly9, SLAMF3) alters SH2 domain binding and T-cell activation. Immunology 146 (3):392-400.
9. de Salort J, Cuenca M, Terhorst C, Engel P, Romero X (2013) Ly9 (CD229) cell-surface receptor is crucial for the development of spontaneous autoantibody production to nuclear antigens. Front Immunol 4:225.
10. Graham DB, et al. (2006) Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM-and SAP-deficient mice. J Immunol 176 (1):291-300.
11. Comte D, Karampetsou MP, Tsokos GC (2015) T cells as a therapeutic target in SLE. Lupus 24 (4-5):351-363.
12. Lieberman LA, Tsokos GC (2010) The IL-2 defect in systemic lupus erythematosus disease has an expansive effect on host immunity. J Biomed Biotechnol 2010:740619.
13. Moulton VR, Grammatikos AP, Fitzgerald LM, Tsokos GC (2013) Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription. Proc Natl Acad Sci USA 110 (5):1845-1850.
14. Bonelli M, et al. (2009) Phenotypic and functional analysis of CD4+ CD25-Foxp3+ T cells in patients with systemic lupus erythematosus. J Immunol 182 (3):1689-1695.
15. Solomou EE, Juang YT, Gourley MF, Kammer GM, Tsokos GC (2001) Molecular basis of deficient IL-2 production in T cells from patients with systemic lupus erythematosus. J Immunol 166 (6):4216-4222.
16. von Spee-Mayer C, et al. (2016) Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis 75 (7): 1407-1415.
17. Sadlack B, et al. (1995) Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur J Immunol 25 (11):3053-3059.
18. Lyssuk EY, Torgashina AV, Soloviev SK, Nassonov EL, Bykovskaia SN (2007) Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. Adv Exp Med Biol 601:113-119.
19. Valencia X, Yarboro C, Illei G, Lipsky PE (2007) Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 178 (4): 2579-2588.
20. Bonelli M, et al. (2008) Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). Int Immunol 20 (7):861-868.
21. Miyara M, et al. (2005) Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol 175 (12):8392-8400.
22. Venigalla RK, et al. (2008) Reduced CD4+,CD25-T cell sensitivity to the suppressive function of CD4+,CD25high,CD127-/low regulatory T cells in patients with active systemic lupus erythematosus. Arthritis Rheum 58 (7):2120-2130.
23. Humrich JY, et al. (2010) Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA 107 (1):204-209.
24. Koga T, et al. (2014) KN-93, an inhibitor of calcium/calmodulin-dependent protein kinase IV, promotes generation and function of Foxp3+ regulatory T cells in MRL/lpr mice. Autoimmunity 47 (7):445-450.
25. Mizui M, et al. (2014) IL-2 protects lupus-prone mice from multiple end-organ damage by limiting CD4-CD8-IL-17-producing T cells. J Immunol 193 (5):2168-2177.
26. Koga T, et al. (2014) CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance. J Clin Invest 124 (5):2234-2245.
27. Humrich JY, et al. (2015) Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis 74 (4):791-792.
28. Saadoun D, et al. (2011) Regulatory T-cell responses to low-dose interleukin-2 in HCVinduced vasculitis. N Engl J Med 365 (22):2067-2077.
29. Koreth J, et al. (2011) Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 365 (22):2055-2066.
30. Klatzmann D, Abbas AK (2015) The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol 15 (5):283-294.
31. Liao W, Lin JX, Leonard WJ (2013) Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38 (1):13-25.
32. Jinnin M, Ihn H, Tamaki K (2006) Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol 69 (2):597-607.
33. Kim HP, Imbert J, Leonard WJ (2006) Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor Rev 17 (5): 349-366.
34. Kim HP, Kim BG, Letterio J, Leonard WJ (2005) Smad-dependent cooperative regulation of interleukin 2 receptor alpha chain gene expression by T cell receptor and transforming growth factor-beta. J Biol Chem 280 (40):34042-34047.
35. Perez-Pinera P, et al. (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods 10 (10):973-976.
36. Sanjana NE, Shalem O, Zhang F (2014) Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods 11 (8):783-784.
37. Tran DQ, Ramsey H, Shevach EM (2007) Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood 110 (8): 2983-2990.
38. Passerini L, et al. (2008) STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25-effector T cells. Int Immunol 20 (3): 421-431.
39. Bilate AM, Lafaille JJ (2012) Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol 30:733-758.
40. Chatterjee M, et al. (2012) Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation. J Immunol 188 (3):1206-1212.
41. Lieberman LA, Tsokos GC (2014) Lupus-prone mice fail to raise antigen-specific T cell responses to intracellular infection. PLoS One 9 (10):e111382.
42. Kis-Toth K, et al. (2015) Selective loss of signaling lymphocytic activation molecule family member 4 CD8 T cells contributes to the decreased cytotoxic cell activity in systemic lupus erythematosus. Arthritis Rheum 68 (1):164-173.
43. Lenardo MJ (1991) Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Nature 353 (6347):858-861.
44. Singer BD, King LS, D'Alessio FR (2014) Regulatory T cells as immunotherapy. Front Immunol 5:46.
45. Tan EM, et al. (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25 (11):1271-1277.