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The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+ eosinophils unique to the small intestine.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 6/7/2022, Vol. 119 Issue 23, p1-9, 19p
- Publication Year :
- 2022
-
Abstract
- C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α<superscript>-</superscript> conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4<superscript>-</superscript> expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4<superscript>+</superscript> eosinophils evinced an immunomodulatory signature, whereas Clec4a4<superscript>-</superscript> eosinophils manifested a proinflammatory profile. Clec4a4<superscript>+</superscript> eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4<superscript>+</superscript> eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 119
- Issue :
- 23
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 157449994
- Full Text :
- https://doi.org/10.1073/pnas.2204557119