Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 104, Issue 3, Pages 447-459Publisher
WILEY
DOI: 10.1002/JLB.4HI0118-017RR
Keywords
airway epithelium; allergic asthma; dust mite; NOD2; Th2
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Funding
- NIH NHLBI [R00 HL122365]
- University of Central Florida
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House dust mites (HDMs) are one of the most significant environmental allergens in the establishment of the so-called Atopic March. It is known that the immune response to HDM is Th2 dominant, but the innate mechanisms leading to HDM-induced type 2 responses are still not completely understood. A number of innate immune receptors have been implicated in the response to HDM including toll-like receptors, C-type lectin receptors, and protease activated receptors. NOD2 is a member of the NOD-like receptor family, which has been reported to be involved in the establishment of type 2 immunity and in blocking respiratory tolerance. NOD2 mediates its effects through its downstream effector kinase, receptor interacting protein (RIP2). It has not been shown if RIP2 is involved in the innate response to HDM and in the resulting generation of type 2 immunity. Furthermore, the role of RIP2 in modulating allergic airway inflammation has been controversial. In this study, we show that RIP2 is activated in airway epithelial cells in response to HDM and is important for the production of CCL2. Using a murine HDM asthma model, we demonstrate that lung pathology, local airway inflammation. inflammatory cytokines. HDM-specific IgG(1) antibody production, and HDM-specific Th2 responses are all reduced in RIP2 knockout mice compared to WT animals. These data illustrate that RIP2 can be activated by a relevant allergic stimulus and that such activation can contribute to allergic airway inflammation. These findings also suggest that RIP2 inhibitors might have some efficacy in down-regulating the inflammatory response in type 2 dominated diseases.
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