Monocyte chemotactic protein–induced protein 1 controls allergic airway inflammation by suppressing IL-5–producing TH2 cells through the Notch/Gata3 pathway

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Asthmatic and allergic inflammation is mediated by TH2 cytokines (IL-4, IL-5, and IL-13). Although we have learned much about how TH2 cells are differentiated, the TH2 checkpoint mechanisms remain elusive.


In this study we investigate how monocyte chemotactic protein–induced protein 1 (MCPIP1; encoded by theZc3h12agene) regulates IL-5–producing TH2 cell differentiation and TH2-mediated inflammation.


The functions ofZc3h12a−/−CD4 T cells were evaluated by checking the expression of TH2 cytokines and transcription factorsin vivoandin vitro. Allergic airway inflammation ofZc3h12a−/−mice was examined with murine asthma models. In addition, antigen-specific CD4 T cells deficient in MCPIP1 were transferred to wild-type recipient mice, challenged with ovalbumin (OVA) or house dust mite (HDM), and accessed for TH2 inflammation.


Zc3h12a−/−mice have spontaneous severe lung inflammation, with an increase in mainly IL-5– and IL-13–producing but not IL-4–producing TH2 cells in the lung. Mechanistically, differentiation of IL-5–producingZc3h12a−/−TH2 cells is mediated through Notch signaling and Gata3 independent of IL-4.Gata3mRNA is stabilizedin Zc3h12a−/−TH2 cells. MCPIP1 promotesGata3mRNA decay through the RNase domain. Furthermore, deletion of MCPIP1 in OVA- or HDM-specific T cells leads to significantly increased TH2-mediated airway inflammation in OVA or HDM murine models of asthma.


Our study reveals that MCPIP1 regulates the development and function of IL-5–producing TH2 cells through the Notch/Gata3 pathway. MCPIP1 represents a new and promising target for the treatment of asthma and other TH2-mediated diseases.

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