IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung.
Interleukin (IL) 31Ralpha (glycoprotein 130-like monocyte receptor and glycoprotein 130-like receptor) heterodimerizes with oncostatin M receptor beta to bind IL-31, a cytokine expressed preferentially by CD4(+) T helper type 2 (Th2) cells. However, the functions of IL-31-IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Ralpha(-/-) mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule alpha(+) cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Ralpha(-/-) mice promoted enhanced ovalbumin-specific CD4(+) T cell proliferation and purified naive CD4(+) T cells from IL-31Ralpha(-/-) mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell- and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4(+) T cell-mediated Th1 responses were normal in IL-31Ralpha(-/-) mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation.
Perrigoue
Jacqueline G
JG
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Li
Ji
J
Zaph
Colby
C
Goldschmidt
Michael
M
Scott
Phillip
P
de Sauvage
Frederic J
FJ
Pearce
Edward J
EJ
Ghilardi
Nico
N
Artis
David
D
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007378:Interleukins / Q000378:metabolism*; D008174:Lung Diseases, Parasitic / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology*
C488159:Il31ra protein, mouse; D018836:Inflammation Mediators; D007378:Interleukins; D018123:Receptors, Interleukin; C502588:interleukin-31, mouse