Regulation of inflammatory responses by IL-17F.
Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.
Yang
Xuexian O
XO
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Chang
Seon Hee
SH
Park
Heon
H
Nurieva
Roza
R
Shah
Bhavin
B
Acero
Luis
L
Wang
Yi-Hong
YH
Schluns
Kimberly S
KS
Broaddus
Russell R
RR
Zhu
Zhou
Z
Dong
Chen
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D020381:Interleukin-17