A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.
Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.
Park
Heon
H
Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
Li
Zhaoxia
Z
Yang
Xuexian O
XO
Chang
Seon Hee
SH
Nurieva
Roza
R
Wang
Yi-Hong
YH
Wang
Ying
Y
Hood
Leroy
L
Zhu
Zhou
Z
Tian
Qiang
Q
Dong
Chen
C
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D060889:Inducible T-Cell Co-Stimulator Protein; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051381:Rats; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D018925:Chemokines; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D020381:Interleukin-17