Getting to the crux of the matter: IL-23 and Th17 cell accumulation in the CNS.
IL-23 plays a critical role in EAE induced by the active immunization of C57BL/6 mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein (MOG(35-55)). It was initially assumed that the pathogenic effects of IL-23 were directly related to the generation, expansion and/or stabilization of autoreactive CD4(+) Th17 cells. However, a number of recent studies have uncovered discrepancies between the requirement for IL-23, as opposed to Th17 cells or their products (IL-17A, IL-17F and IL-22), in the development of EAE. In this issue of the European Journal of Immunology, it is demonstrated that impairment of IL-23 signaling does not impede the expansion of myelin-specific CD4(+) T cells in peripheral lymphoid tissues but inhibits their accumulation in the CNS. This paper contributes to a growing body of data that implicates IL-23 in the acquisition of CNS homing properties by autoreactive effector cells.
Segal
Benjamin M
BM
Department of Neurology, University of Michigan, Ann Arbor, 48109, USA. bmsegal@med.umich.edu
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D020381:Interleukin-17; D053759:Interleukin-23; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; C528688:interleukin-23 receptor, mouse