The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo.
Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17-producing helper T cells (T(H)-17 cells) and has been linked to many human immune disorders. Here we restricted deficiency in the IL-23 receptor to defined cell populations in vivo to investigate the requirement for IL-23 signaling in the development and function of T(H)-17 cells in autoimmunity, inflammation and infection. In the absence of IL-23, T(H)-17 development was stalled at the early activation stage. T(H)-17 cells failed to downregulate IL-2 and also failed to maintain IL-17 production or upregulate expression of the IL-7 receptor alpha-chain. These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues.
McGeachy
Mandy J
MJ
Schering-Plough Biopharma, Palo Alto, California 94304, USA.
Chen
Yi
Y
Tato
Cristina M
CM
Laurence
Arian
A
Joyce-Shaikh
Barbara
B
Blumenschein
Wendy M
WM
McClanahan
Terrill K
TK
O'Shea
John J
JJ
Cua
Daniel J
DJ
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000172:deficiency / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000276:immunology
D020381:Interleukin-17; D007376:Interleukin-2; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C528688:interleukin-23 receptor, mouse