A key requirement for CD300f in innate immune responses of eosinophils in colitis
Autor: | Michal Itan, Itay Moshkovits, Chen Varol, Hadar Reichman, Maria Lampinen, Ariel Munitz, N. Ben Baruch-Morgenstern, Ehud Zigmond, Danielle Karo-Atar, Perri Rozenberg, Lee A. Denson, Marie Carlson, Y. Haberman |
---|---|
Rok vydání: | 2017 |
Předmět: |
Adult
Male 0301 basic medicine Immunology Inflammation Biology Mice Young Adult 03 medical and health sciences Th2 Cells 0302 clinical medicine Immune system Crohn Disease Immunity medicine Animals Humans Immunology and Allergy Calgranulin A Receptors Immunologic Cells Cultured Mice Knockout Innate immune system Monocyte Innate lymphoid cell Middle Aged Eosinophil Immunity Innate Eosinophils Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Mucosal immunology Colitis Ulcerative Female medicine.symptom 030215 immunology |
Zdroj: | Mucosal Immunology. 10:172-183 |
ISSN: | 1933-0219 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |