Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells

FASEB Journal

Volumn 24, Issue 5, 2010, Pages 1583-1592

  Xu, Hongwei ^a,b,c   Wu, Zhi Ying ^a,b,h   Fang, Fang ^a,b   Guo, Lan ^a,b   Chen, Doris ^a,b   Chen, John Xi ^d   Stern, David ^e   Taylor, Gregory A ^f,g   Jiang, Hong ^b   Yan, Shirley ShiDu ^a,b  

^a NewYork Presbyterian Hospital   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c HARBIN MEDICAL UNIVERSITY   (China)

^d MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^e UNIVERSITY OF CINCINNATI   (United States)

^f DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g DURHAM VA MEDICAL CENTER   (United States)

^h FUDAN UNIVERSITY   (China)

Author keywords

Animal model; EAE MS; IFN mediated apoptosis

Indexed keywords

INTERFERON; MYELIN BASIC PROTEIN; GAMMA INTERFERON; GUANINE NUCLEOTIDE BINDING PROTEIN; IFI1 PROTEIN, MOUSE;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CD4+ T LYMPHOCYTE; CENTRAL NERVOUS SYSTEM; GENE; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IRGM1 GENE; MONONUCLEAR PHAGOCYTE; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; SPLEEN; UPREGULATION; ANIMAL; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MOUSE MUTANT; SPINAL CORD;

ANIMALIA; MUS;

ANIMALS; APOPTOSIS; CD4-POSITIVE T-LYMPHOCYTES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GTP-BINDING PROTEINS; HUMANS; INTERFERON-GAMMA; LYMPHOCYTE ACTIVATION; MICE; MICE, KNOCKOUT; SPINAL CORD;

EID: 77952304848     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.09-137323     Document Type: Article

References (33)

1. Sospedra, M., and Martin, R. (2005) Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683-747
2. Hohlfeld, R., and Wekerle, H. (2001) Immunological update on multiple sclerosis. Curr. Opin. Neurol. 14, 299-304
3. Zamvil, S., Nelson, P., Trotter, J., Mitchell, D., Knobler, R., Fritz, R., and Steinman, L. (1985) T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317, 355-358
4. Mao, P., and Reddy, P. H. (2010) Is multiple sclerosis a mitochondrial disease? Biochim. Biophys. Acta 1802, 66-79
5. Refaeli, Y., Van Parijs, L., Alexander, S. I., and Abbas, A. K. (2002) Interferon gamma is required for activation-induced death of T lymphocytes. J. Exp. Med. 196, 999-1005
6. Dalton, D. K., Haynes, L., Chu, C. Q., Swain, S. L., and Wittmer S. (2000) Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells. J. Exp. Med. 192, 117-122
7. Chu, C. Q., Wittmer, S., and Dalton, D. K. (2000) Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J. Exp. Med. 192, 123-128
8. Feng, C. G., Weksberg, D. C., Taylor, G. A., Sher, A., and Goodell, M. A. (2008) The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation. Cell Stem Cell 2, 83-89
9. Taylor, G. A., Feng, C. G., and Sher, A. (2004) p47 GTPases: regulators of immunity to intracellular pathogens. Nat. Rev. Immunol. 4, 100-109 (Pubitemid 38209204)
10. Taylor, G. A., Jeffers, M., Largaespada, D. A., Jenkins, N. A., Copeland, N. G., and Woude, G. F. (1996) Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma. J. Biol. Chem. 271, 20399-20405
11. MacMicking, J.D. IFN-inducible GTPases and immunity to intracellular pathogens. (2004) Trends Immunol. 25, 601-609
12. Santiago, H. C., Feng, C. G., Bafica, A., Roffe, E., Arantes, R. M., Cheever, A., Taylor, G., Vieira, L. Q., Aliberti, J., Gazzinelli, R. T., and Sher, A. (2005) Mice deficient in LRG-47 display enhanced susceptibility to trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth. J. Immunol. 175, 8165-8172
13. Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., and Deretic V. (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753-766
14. MacMicking, J. D., Taylor, G. A., and McKinney, J. D. (2003) Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science 302, 654-659
15. Singh, S. B., Davis, A. S., Taylor, G. A., and Deretic, V. (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438-1441
16. Yan, S. S., Wu, Z. Y., Zhang, H. P., Furtado, G., Chen, X., Yan, S. F., Schmidt, A. M., Brown, C., Stern, A., LaFaille, J., Chess, L., Stern, D. M., and Jiang, H. (2003) Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat. Med. 9, 287-293
17. Du Yan, S., Zhu, H., Fu, J., Yan, S. F., Roher, A., Tourtellotte, W. W., Rajavashisth, T., Chen, X., Godman, G. C., Stern, D., and Schmidt, A. M. (1997) Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 94, 5296-5301
18. Arancio, O., Zhang, H. P., Chen, X., Lin, C., Trinchese, F., Puzzo, D., Liu, S., Hegde, A., Yan, S.F., Stern, A., Luddy, J. S., Lue, L. F., Walker, D. G., Roher, A., Buttini, M., Mucke, L., Li, W., Schmidt, A. M., Kindy, M., Hyslop, P. A., Stern, D. M., and Du Yan, S. S. (2004) RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 23, 4096-4105
19. O'Connor, R. A., Wittmer, S., and Dalton, D. K. (2005) Infection-induced apoptosis deletes bystander CD4+ T cells: a mechanism for suppression of autoimmunity during BCG infection. J. Autoimmun. 24, 93-100
20. Mahoney, J. A., and Rosen, A. (2005) Apoptosis and autoimmunity. Curr. Opin. Immunol. 17, 583-588
21. Todaro, M., Zeuner, A., and Stassi, G. (2004) Role of apoptosis in autoimmunity. J. Clin. Immunol. 24, 1-11
22. Gold, R., Hartung, H. P., and Lassmann, H. (1997) T-cell apoptosis in autoimmune diseases: termination of inflammation in the nervous system and other sites with specialized immunedefense mechanisms. Trends Neurosci. 20, 399-404
23. Pender, M. P., Nguyen KB., McCombe, P. A., and Kerr, J. F. (1991) Apoptosis in the nervous system in experimental allergic encephalomyelitis. J. Neurol. Sci. 104, 81-87
24. Tabi, Z., McCombe, P. A., and Pender, M. P. (1994) Apoptotic elimination of V beta 8.2+ cells from the central nervous system during recovery from experimental autoimmune encephalomyelitis induced by the passive transfer of V beta 8.2+ encephalitogenic T cells. Eur. J. Immunol. 24, 2609-2617 (Pubitemid 2149919)
25. Krakowski, M., and Owens, T. (1996) Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur. J. Immunol. 26, 1641-1646
26. Ferber, I. A., Brocke, S., Taylor-Edwards, C., Ridgway, W., Dinisco, C., Steinman, L., Dalton, D., and Fathman C. G. (1996) Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 156, 5-7
27. Hur, E. M., Youssef, S., Haws, M. E., Zhang, S. Y., Sobel, R. A., and Steinman, L. (2007) Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat. Immunol. 8, 74-83
28. Stromnes, I. M., and Goverman, J. M. (2007) Osteopontin-induced survival of T cells. Nat. Immunol. 8, 19-20
29. Collazo, C. M., Yap, G. S., Sempowski, G. D., Lusby, K. C., Tessarollo, L., Woude, G. F., Sher, A., and Taylor, G. A. (2001) Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection. J. Exp. Med. 194, 181-188
30. Butcher, B. A., Del Rio, L., Butcher, B. A., Mogensen, T. H., Paludan, S. R., Flavell, R. A., and Denkers, E. Y. (2005) p47 GTPases regulate Toxoplasma gondii survival in activated macrophages. Infect. Immun. 73, 3278-3286
31. Feng, C. G., Collazo-Custodio, C. M., Eckhaus, M., Hieny, S., Belkaid, Y., Elkins, K., Jankovic, D., Taylor, G. A., and Sher A. (2004) Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia. J. Immunol. 172, 1163-1168
32. Zhang, H. M., Yuan, J., Cheung, P., Luo, H,. Yanagawa, B., Chau, D., Stephan-Tozy, N., Wong, B. W., Zhang, J., Wilson, J. E., McManus, B. M., and Yang D. (2003) Overexpression of interferon-gamma-inducible GTPase inhibits coxsackievirus B3-induced apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway and inhibition of viral replication. J. Biol. Chem. 278, 33011-33019
33. Feng, C. G., Zheng, L., Jankovic, D., Báfica, A., Cannons, J. L., Watford, W. T., Chaussabel, D., Hieny, S., Caspar, P., Schwartzberg, P. L., Lenardo, M. J., and Sher, A. (2008) The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death. Nat. Immunol. 9, 1279-1287