The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity

Nature Immunology

Volumn 17, Issue 4, 2016, Pages 433-440

  Gonzalez Martin, Alicia ^a   Adams, Brian D ^b   Lai, Maoyi ^a   Shepherd, Jovan ^a   Salvador Bernaldez, Maria ^c   Salvador, Jesus M ^c   Lu, Jun ^b   Nemazee, David ^a   Xiao, Changchun ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

B CELL ANTIGEN RECEPTOR; B LYMPHOCYTE ANTIGEN; BIM PROTEIN; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45 ALPHA; LYMPHOCYTE ANTIGEN RECEPTOR; MICRORNA; MICRORNA 148A; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; BCL2L11 PROTEIN, HUMAN; BCL2L11 PROTEIN, MOUSE; CELL CYCLE PROTEIN; GADD45A PROTEIN, MOUSE; MEMBRANE PROTEIN; MIRN148 MICRORNA, MOUSE; NUCLEAR PROTEIN; ONCOPROTEIN; PTEN PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; CELL SURVIVAL; CONTROLLED STUDY; HUMAN; HUMAN CELL; IN VIVO STUDY; LYMPHOCYTE; MOUSE; NONHUMAN; PRE B LYMPHOCYTE; PRIORITY JOURNAL; ANIMAL; APOPTOSIS; BONE MARROW TRANSPLANTATION; CELL PROLIFERATION; DISEASE MODEL; GENETICS; HEK293 CELL LINE; IMMUNOBLOTTING; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; METABOLISM; MURPHY ROTHS LARGE LYMPHOPROLIFERATIVE MOUSE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; SYSTEMIC LUPUS ERYTHEMATOSUS;

ANIMALS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOIMMUNITY; B-LYMPHOCYTES; BCL-2-LIKE PROTEIN 11; BONE MARROW TRANSPLANTATION; CELL CYCLE PROTEINS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; HEK293 CELLS; HUMANS; IMMUNE TOLERANCE; IMMUNOBLOTTING; LUPUS ERYTHEMATOSUS, SYSTEMIC; MEMBRANE PROTEINS; MICE; MICE, INBRED MRL LPR; MICRORNAS; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS; PTEN PHOSPHOHYDROLASE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS, RNA;

EID: 84959076294     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3385     Document Type: Article

References (50)

1. Shlomchik, M.J. Sites and stages of autoreactive B cell activation and regulation. Immunity 28, 18-28 (2008
2. Goodnow, C.C., Sprent, J., Fazekas de St Groth, B. & Vinuesa, C.G. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435, 590-597 (2005
3. Nemazee, D. Receptor editing in lymphocyte development and central tolerance. Nat. Rev. Immunol. 6, 728-740 (2006
4. Tiller, T., et al. Autoreactivity in human IgG+ memory B cells. Immunity 26, 205-213 (2007
5. Wardemann, H., et al. Predominant autoantibody production by early human B cell precursors. Science 301, 1374-1377 (2003
6. Kinnunen, T., et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J. Clin. Invest. 123, 2737-2741 (2013
7. Samuels, J., Ng, Y.S., Coupillaud, C., Paget, D. & Meffre, E. Impaired early B cell tolerance in patients with rheumatoid arthritis. J. Exp. Med. 201, 1659-1667 (2005
8. Yurasov, S., et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J. Exp. Med. 201, 703-711 (2005
9. Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233 (2009
10. Kuchen, S., et al. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity 32, 828-839 (2010
11. Monticelli, S., et al. MicroRNA profiling of the murine hematopoietic system. Genome Biol. 6, R71 (2005
12. O'Connell, R.M., Rao, D.S., Chaudhuri, A.A. & Baltimore, D. Physiological and pathological roles for microRNAs in the immune system. Nat. Rev. Immunol. 10, 111-122 (2010
13. Xiao, C. & Rajewsky, K. MicroRNA control in the immune system: basic principles. Cell 136, 26-36 (2009
14. Chauhan, S.K., Singh, V.V., Rai, R., Rai, M. & Rai, G. Differential microRNA profile and post-transcriptional regulation exist in systemic lupus erythematosus patients with distinct autoantibody specificities. J. Clin. Immunol. 34, 491-503 (2014
15. Pan, W., et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J. Immunol. 184, 6773-6781 (2010
16. Stagakis, E., et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann. Rheum. Dis. 70, 1496-1506 (2011
17. Te, J.L., et al. Identification of unique microRNA signature associated with lupus nephritis. PLoS One 5, e10344 (2010
18. Dai, R., et al. Identification of a common lupus disease-Associated microRNA expression pattern in three different murine models of lupus. PLoS One 5, e14302 (2010
19. Lindberg, R.L., Hoffmann, F., Mehling, M., Kuhle, J. & Kappos, L. Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur. J. Immunol. 40, 888-898 (2010
20. Qin, H.H., et al. The expression and significance of miR-17-92 cluster miRs in CD4+ T cells from patients with systemic lupus erythematosus. Clin. Exp. Rheumatol. 31, 472-473 (2013
21. Simpson, L.J., et al. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat. Immunol. 15, 1162-1170 (2014
22. Kang, S.G., et al. MicroRNAs of the miR-17~92 family are critical regulators of T(FH) differentiation. Nat. Immunol. 14, 849-857 (2013
23. Xiao, C., et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat. Immunol. 9, 405-414 (2008
24. Luo, X., et al. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet. 7, e1002128 (2011
25. Tang, Y., et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 60, 1065-1075 (2009
26. Boldin, M.P., et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J. Exp. Med. 208, 1189-1201 (2011
27. Hu, R., et al. miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity 41, 605-619 (2014
28. Lu, L.F., et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142, 914-929 (2010
29. Adams, B.D., et al. An in vivo functional screen uncovers miR-150-mediated regulation of hematopoietic injury response. Cell Rep. 2, 1048-1060 (2012
30. Duong, B.H., et al. Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape. J. Immunol. 187, 5596-5605 (2011
31. Lu, R., Neff, N.F., Quake, S.R. & Weissman, I.L. Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding. Nat. Biotechnol. 29, 928-933 (2011
32. Haftmann, C., et al. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim. Eur. J. Immunol. 45, 1192-1205 (2015
33. Dai, R., et al. Sex differences in the expression of lupus-Associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol. Sex Differ. 4, 19 (2013
34. Scott, D.W., Livnat, D., Pennell, C.A. & Keng, P. Lymphoma models for B cell activation and tolerance. III. Cell cycle dependence for negative signalling of WEHI-231 B lymphoma cells by anti-mu. J. Exp. Med. 164, 156-164 (1986
35. Scott, D.W., et al. Lymphoma models for B-cell activation and tolerance. II. Growth inhibition by anti-mu of WEHI-231 and the selection and properties of resistant mutants. Cell. Immunol. 93, 124-131 (1985
36. Bouillet, P., et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286, 1735-1738 (1999
37. Erickson, S.L., et al. Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature 372, 560-563 (1994
38. Lesche, R., et al. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32, 148-149 (2002
39. Rickert, R.C., Roes, J. & Rajewsky, K. B lymphocyte-specific, Cre-mediated mutagenesis in mice. Nucleic Acids Res. 25, 1317-1318 (1997
40. Salvador, J.M., et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 16, 499-508 (2002
41. Enders, A., et al. Loss of the pro-Apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells. J. Exp. Med. 198, 1119-1126 (2003
42. Cheng, S., et al. BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten. Cell Res. 19, 196-207 (2009
43. Andrews, B.S., et al. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J. Exp. Med. 148, 1198-1215 (1978
44. Shen, N., Liang, D., Tang, Y., de Vries, N. & Tak, P.P. MicroRNAs-novel regulators of systemic lupus erythematosus pathogenesis. Nat. Rev. Rheumatol. 8, 701-709 (2012
45. Di Cristofano, A., et al. Impaired Fas response and autoimmunity in Pten+/- mice. Science 285, 2122-2125 (1999
46. Oliver, P.M., Vass, T., Kappler, J. & Marrack, P. Loss of the proapoptotic protein, Bim, breaks B cell anergy. J. Exp. Med. 203, 731-741 (2006
47. Browne, C.D., Del Nagro, C.J., Cato, M.H., Dengler, H.S. & Rickert, R.C. Suppression of phosphatidylinositol 3, 4, 5-trisphosphate production is a key determinant of B cell anergy. Immunity 31, 749-760 (2009
48. Salvador, J.M., Brown-Clay, J.D. & Fornace, A.J. Jr. Gadd45 in stress signaling, cell cycle control, and apoptosis. Adv. Exp. Med. Biol. 793, 1-19 (2013
49. Salvador, J.M., Mittelstadt, P.R., Belova, G.I., Fornace, A.J. Jr. & Ashwell, J.D. The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway. Nat. Immunol. 6, 396-402 (2005
50. Tong, T., et al. Gadd45a expression induces Bim dissociation from the cytoskeleton and translocation to mitochondria. Mol. Cell. Biol. 25, 4488-4500 (2005