A protective function for interleukin 17A in   T cell-mediated intestinal inflammation.
Interleukin 23 (IL-23) and IL-17 have been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Yet as an important function for IL-23 is emerging, the function of IL-17 in inflammatory bowel disease remains unclear. Here we demonstrate IL-17A-mediated protection in the CD45RBhi transfer model of colitis. An accelerated wasting disease elicited by T cells deficient in IL-17A correlated with higher expression of genes encoding T helper type 1-type cytokines in colon tissue. IL-17A also modulated T helper type 1 polarization in vitro. Furthermore, T cells deficient in the IL-17 receptor elicited an accelerated, aggressive wasting disease relative to that elicited by wild-type T cells in recipient mice. Our data demonstrate a protective function for IL-17 and identify T cells as not only the source but also a target of IL-17 in vivo.
O'Connor
William
W
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kamanaka
Masahito
M
Booth
Carmen J
CJ
Town
Terrence
T
Nakae
Susumu
S
Iwakura
Yoichiro
Y
Kolls
Jay K
JK
Flavell
Richard A
RA
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007371:Interferon-gamma; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000276:immunology; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D019282:Wasting Syndrome / Q000276:immunology*; D000098815:T-bet Transcription Factor
C098680:Il17a protein, mouse; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens