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IL-31-IL-31R interactions
negatively regulate type 2 inflammation in the lung
Perrigoue JG, Li J, Zaph C, Goldschmidt M, Scott
P, Pearce EJ, de Sauvage FJ, Ghilardi N and
D Artis. (2007) J. Exp. Med. 204: 481-487.
IL-31Rα (GLMR, GPL) heterodimerizes with OSMRß 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. Following intravenous injection of Schistosoma
mansoni eggs, IL-31Rα-/- mice developed severe
pulmonary inflammation, characterized by an increase in the
area of granulomatous inflammation, increased numbers of
RELM-α+
cells, and enhanced collagen deposition compared to WT counterparts. In
vitro, macrophages generated from IL-31Rα-/- mice promoted
enhanced OVA-specific CD4+ T cell proliferation and purified
naïve CD4+ T cells from IL-31Rα-/- 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-31Rα-/-
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. |
