The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+ eosinophils unique to the small intestine

Wei Le Wang, Jun Kasamatsu, Satoru Joshita, Susan Gilfillan, Blanda Di Luccia, Santosh K. Panda, Do Hyun Kim, Pritesh Desai, Jennifer K. Bando, Stanley Ching Cheng Huang, Kentaro Yomogida, Hitomi Hoshino, Mana Fukushima, Elizabeth A. Jacobsen, Steven J. Van Dyken, Christiane Ruedl, Marina Cella, Marco Colonna

Research output: Contribution to journalArticlepeer-review

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 CD8α2 conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a42 eosinophils manifested a proinflammatory profile. Clec4a4+ 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+ 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.

Original languageEnglish
Article numbere2204557119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number23
DOIs
StatePublished - Jun 7 2022

Keywords

  • allergy
  • aryl hydrocarbon receptor
  • eosinophil
  • helminth
  • intestine

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