A key requirement for CD300f in innate immune responses of eosinophils in colitis.
Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f-/-mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f-/-mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Moshkovits
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Reichman
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Karo-Atar
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Rozenberg
Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Zigmond
Department of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|Division of Pediatric Gastroenterology, Hepatology and Nutrition, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
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Haberman
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Ben Baruch-Morgenstern
Gastroenterology Research Group, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
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Lampinen
Gastroenterology Research Group, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
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Carlson
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Itan
Department of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
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Denson
Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Varol
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Munitz
D000328:Adult; D000818:Animals; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
C519443:CD300LF protein, human; C482560:CLM-1 protein, mouse; D040501:Calgranulin A; D011971:Receptors, Immunologic