Membrane-associated RING-CH-1 (MARCH1) is an E3 ubiquitin ligase which targets MHC-II, CD86 and various other molecules for degradation. It is one of the most efficient post-translational regulators of antigen presentation. MARCH1 is expressed in resting immature dendritic cells and B cells but can be induced in other cell types. While activation of most immune cells results in a reduction in MARCH1 gene expression, its anti-inflammatory properties are highlighted by its induction in response to IL-10. Here, we review what is known about the regulation of MARCH1 gene expression in response to IL-10 by various immune cells. We speculate on the role of MARCH1 ininfection, its differential expression pattern and the promise that this E3 ubiquitin ligase holds to influence immune responses and mitigate immune pathologies.
Coscoy, L. and Ganem, D. (2000) Kaposi’s sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proceedings of the National Academy of Sciences of USA, 97, 8051-8056. doi:10.1073/pnas.140129797
Ishido, S., Wang, C., Lee, B.S., Cohen, G.B. and Jung, J.U. (2000) Down-regulation of major histocompatibility complex class I molecules by Kaposi’s sarcoma-associated herpesvirus K3 and K5 proteins. Journal of Virology, 74, 5300-5309. doi:10.1128/JVI.74.11.5300-5309.2000
Stevenson, P.G,. Efstathiou, S., Doherty, P.C. and Lehner, P.J. (2000) Inhibition of MHC class I-restricted antigen presentation by gamma 2-herpesviruses. Proceedings of the National Academy of Sciences of USA, 97, 8455-8460. doi:10.1073/pnas.150240097
Bartee, E., Mansouri, M., Hovey Nerenberg, Gouveia, B.T.K. and Fruh K. (2004) Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. Journal of Virology, 78, 1109-1120. doi:10.1128/JVI.78.3.1109-1120.2004
Goto, E., Ishido, S., Sato, Y., Ohgimoto, S., Ohgimoto, K., Nagano-Fujii, M. et al. (2003) c-MIR, a human E3 ubiquitin ligase, is a functional homolog of herpesvirus proteins MIR1 and MIR2 and has similar activity. Journal of Biological Chemistry, 278, 14657-14658. doi:10.1074/jbc.M211285200
Moore, K.W., de Waal, M.R., Coffman, R.L. and O’Garra, A. (2001) Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology, 19, 683-765. doi:10.1146/annurev.immunol.19.1.683
Pestka, S., Krause, C.D., Sarkar, D., Walter, M.R., Shi, Y. and Fisher, P.B. (2004) Interleukin-10 and related cytokines and receptors. Annual Review of Immunology, 22, 929-979. doi:10.1146/annurev.immunol.22.012703.104622
de Waal, M.R., Abrams, J., Bennett, B., Figdor, C.G. and De Vries, J.E. (1991) Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. Journal of Experimental Medicine, 174, 1209-1220. doi:10.1084/jem.174.5.1209
Fiorentino, D.F., Zlotnik, A., Mosmann, T.R., Howard, M. and O’Garra, A. (1991) IL-10 inhibits cytokine production by activated macrophages. Journal of Immunology, 147, 3815-3822.
Gruber, M.F., Williams, C.C. and Gerrard, T.L. (1994) Macrophage-colony-stimulating factor expression by anti-CD45 stimulated human monocytes is transcriptionally up-regulated by IL-1 beta and inhibited by IL-4 and IL-10. Journal of Immunology, 152, 1354-1361.
Murray, P.J. (2006) Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Current Opinion in Pharmacology, 6, 379-386. doi:10.1016/j.coph.2006.01.010
Berkman, N., John, M., Roesems, G., Jose, P.J., Barnes, P.J. and Chung, K.F. (1995) Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages. Journal of Immunology, 155, 4412-4418.
Kopydlowski, K.M., Salkowski, C.A., Cody, M.J., van R.N., Major, J., Hamilton, T.A., et al. (1999) Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. Journal of Immunology, 163, 1537-1544.
Matsuki, Y., Ohmura-Hoshino, M., Goto, E., Aoki, M., Mito-Yoshida, M., Uematsu, M., et al. (2007) Novel regulation of MHC class II function in B cells. EMBO Journal, 26, 846-854. doi:10.1038/sj.emboj.7601556
Bartee, E., Eyster, C.A., Viswanathan, K., Mansouri, M., Donaldson, J.G. and Fruh, K. (2010) Membrane-Associated RING-CH proteins associate with Bap31 and target CD81 and CD44 to lysosomes. PLoS One, 5, e15132. doi:10.1371/journal.pone.0015132
Thibodeau, J., Bourgeois-Daigneault, M.C., Huppe, G., Tremblay, J., Aumont, A., Houde, M., et al. (2008) Inter-leukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. European Journal of Immunology, 38, 1225-1230. doi:10.1002/eji.200737902
Galbas, T., Steimle, V., Lapointe, R., Ishido, S. and Thibodeau, J. (2012) MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression. Cytokine, 59, 27-30. doi:10.1016/j.cyto.2012.03.015
Hunt, D., Wilson, J.E., Weih, K.A., Ishido, S., Harton, J.A., Roche, P.A., et al. (2012) Francisella tularensis elicits IL-10 via a PGE(2)-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation. PLoS ONE, 7, e37330. doi:10.1371/journal.pone.0037330
Corcoran, K., Jabbour, M., Bhagwandin, C., Deymier, M.J., Theisen, D.L. and Lybarger, L. (2011) Ubiquitin-mediated regulation of CD86 protein expression by the ubiquitin ligase membrane-associated RING-CH-1 (MA-RCH1). Journal of Biological Chemistry, 286, 37168-37180. doi:10.1074/jbc.M110.204040
Jabbour, M., Campbell, E.M., Fares, H. and Lybarger, L. (2009) Discrete domains of MARCH1 mediate its localization, functional interactions, and posttranscriptional control of expression. Journal of Immunology, 183, 6500-6512. doi:10.4049/jimmunol.0901521
Tze, L.E., Horikawa, K., Domaschenz, H., Howard, D.R., Roots, C.M., Rigby, R.J., et al. (2011) CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. Journal of Experimental Medicine, 208, 149-165. doi:10.1084/jem.20092203
Wolk, K., Witte, E., Reineke, U., Witte, K., Friedrich, M., Sterry, W., et al. (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes & Immunity, 6, 8-18.
Kunz, S., Wolk, K., Witte, E., Witte, K., Doecke. W.D., Volk, H.D., et al. (2006) Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Experimental Dermatology, 15, 991-1004. doi:10.1111/j.1600-0625.2006.00516.x
Kitamura, H., Kamon, H., Sawa, S., Park, S.J., Katunuma, N., Ishihara, K., et al. (2005) IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells. Immunity, 23, 491-502. doi:10.1016/j.immuni.2005.09.010
Koppelman, B., Neefjes, J.J., De Vries, J.E. and Malefyt, R.D. (1997) Interleukin-10 down-regulates MHC class II peptide complexes at the plasma membrane of monocytes by affecting arrival and recycling. Immunity, 7, 861-871. doi:10.1016/S1074-7613(00)80404-5
De Gassart, A., Camosseto, V., Thibodeau, J., Ceppi, M., Catalan, N., Pierre, P., et al. (2008) MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proceedings of the National Academy of Sciences of USA, 105, 3491-3496. doi:10.1073/pnas.0708874105
Young, L.J., Wilson, N.S., Schnorrer, P., Proietto, A., Ten, B.T., Matsuki, Y., et al. (2008) Differential MHC class II synthesis and ubiquitination confers distinct antigen presenting properties on conventional and plasmacytoid dendritic cells. Nature Immunology, 9, 1244-1252. doi:10.1038/ni.1665
Ten, B.T., de Graaff, A., van’t Veld, E.M., Wauben, M.H., Stoorvogel, W. and Wubbolts, R. (2010) Trafficking of MHC class II in dendritic cells is dependent on but not regulated by degradation of its associated invariant chain. Traffic, 11, 324-331. doi:10.1111/j.1600-0854.2009.01024.x
Yusof, W.N., Nagaratnam, M., Koh, C.L., Puthucheary, S. and Pang, T. (1993) Release of prostaglandin E2 by human mononuclear cells exposed to heat-killed Salmonella typhi. Microbiology and Immunology, 37, 667-670.
Rangel, M.J., Estrada, G.I,, De La Luz, G.H., Aguilar, L.D., Marquez, R. and Hernandez, P.R. (2002) The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis. Immunology, 106, 257-266.
N’Guessan, P.D., Etouem, M.O., Schmeck, B., Hocke, A.C., Scharf, S., Vardarova, K., et al. (2007) Legionella pneumophila-induced PKCalpha-, MAPK-, and NF-kappaB-dependent COX-2 expression in human lung epithetlium. American Journal of Physiology: Lung Cellular and Molecular, 292, L267-L277. doi:10.1152/ajplung.00100.2006
Hillhouse, E.E., Beauchamp, C., Chabot-Roy, G., Dugas, V. and Lesage, S. (2010) Interleukin-10 limits the expansion of immunoregulatory CD4-CD8-T cells in autoimmune-prone non-obese diabetic mice. Immunology & Cell Biology, 88, 771-780. doi:10.1038/icb.2010.84
Draghi, N.A. and Denzin, L.K.. (2010) H2O, a MHC class II-like protein, sets a threshold for B-cell entry into germinal centers. Proceedings of the National Academy of Sciences of USA, 107, 16607-16612. doi:10.1073/pnas.1004664107
Hofmann, S.R., Rosen-Wolff, A., Tsokos, G.C. and Hedrich, C.M. (2012) Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury. Clinical Immunology, 143, 116-127. doi:10.1016/j.clim.2012.02.005
Bourgeois-Daigneault, M.C. and Thibodeau, J. (2012) Autoregulation of MARCH1 expression by dimerization and autoubiquitination. Journal of Immunology, 188, 4959-4970. doi:10.4049/jimmunol.1102708
Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. and Muller, W. (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell, 75, 263-274. doi:10.1016/0092-8674(93)80068-P