IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung
Jacqueline G Perrigoue1, Ji Li, Colby Zaph
1Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
The Journal of Experimental Medicine
|March 14, 2007
Summary
Interleukin-31 receptor alpha (IL-31Ralpha) signaling limits type 2 inflammation. IL-31Ralpha-deficient mice show severe lung inflammation, indicating IL-31Ralpha
Area of Science:
- Immunology
- Inflammation Biology
- Respiratory Medicine
Background:
- Interleukin-31 receptor alpha (IL-31Ralpha) forms a heterodimer with oncostatin M receptor beta, binding Interleukin-31 (IL-31).
- IL-31 is a cytokine predominantly produced by CD4(+) T helper type 2 (Th2) cells.
- The precise roles of IL-31-IL-31R signaling in immune regulation are not fully understood.
Purpose of the Study:
- To investigate the function of IL-31R signaling in immune regulation.
- To determine the role of IL-31R in type 2 inflammation, particularly in the lung.
Main Methods:
- Utilized IL-31Ralpha knockout (IL-31Ralpha(-/-)) and wild-type (WT) mice.
- Administered Schistosoma mansoni eggs intravenously to induce lung inflammation.
- Performed in vitro assays using macrophages and CD4(+) T cells from knockout and WT mice.
Main Results:
- IL-31Ralpha(-/-) mice exhibited exacerbated pulmonary inflammation, characterized by larger granulomas, increased resistin-like molecule alpha (RELMα) positive cells, and heightened collagen deposition.
- Macrophages from IL-31Ralpha(-/-) mice enhanced ovalbumin-specific CD4(+) T cell proliferation.
- Naive CD4(+) T cells from IL-31Ralpha(-/-) mice showed increased proliferation and Th2 cytokine expression.
- Th1 responses remained unaffected in IL-31Ralpha(-/-) mice.
Conclusions:
- IL-31R signaling acts as a novel negative regulator of type 2 inflammation in the lung.
- This regulatory function is specific to type 2 immune responses, not affecting Th1 responses.
- IL-31R signaling exerts regulatory control intrinsically within T cells and macrophages.
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