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CD43 contributes to mouse Th17 cell adhesion to intercellular adhesion molecule‐1
Author(s) -
Velazquez Francisco Esteban,
Salvador Ane,
Nevers Tania,
Alcaide Pilar
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.57.9
Subject(s) - experimental autoimmune encephalomyelitis , cell adhesion molecule , myelin oligodendrocyte glycoprotein , selectin , cell adhesion , microbiology and biotechnology , chemistry , inflammation , intercellular adhesion molecule 1 , encephalomyelitis , cd43 , immunology , adhesion , biology , antigen , multiple sclerosis , cd20 , organic chemistry
CD43 is a sialoglycoprotein with many functions and roles that can serve as a pro‐adhesive and anti‐adhesive molecule. In T cells, CD43 has been shown to function as an E‐selectin (E‐sel) ligand in cooperation with PSGL‐1. We recently demonstrated that CD43 functions as an E‐sel ligand for T helper 17 (Th17) cells, which participate in autoimmunity and in chronic inflammatory reactions when recruited at sites of inflammation. Moreover, CD43 −/− mice are protected from Experimental Autoimmune Encephalomyelitis (EAE) and have decreased Th17 cell recruitment into the spinal cord. Interestingly, E‐sel is not required for the development of EAE, and other adhesion molecules such as intracellular adhesion molecule 1 (ICAM‐1) and vascular cellular adhesion molecule 1 (VCAM‐1) mediate T cell recruitment in EAE instead. Despite the subset specific use of CD43 as an E‐sel ligand by Th17 cells, other potential pro‐adhesive and anti‐adhesive properties of CD43 on Th17 cells to adhesion molecules such as ICAM‐1 and VCAM‐1 have yet to be properly characterized. We hypothesize that Th17 cells use CD43 as a pro‐adhesive molecule to adhere to other adhesion molecules and infiltrate the spinal cord in EAE in an E‐selectin ligand independent manner. We use real‐time live video microscopy under flow conditions, Th17 cells generated in vitro from WT and CD43 −/− mice, and the experimental autoimmune encephalomyelitis (EAE) model of autoimmunity and inflammation. We report that upon immunization with myelin oligodendrocyte glycoprotein (MOG), ICAM‐1 was upregulated in the spinal cord of WT and CD43 −/− mice, in contrast with E‐sel, which had undetectable levels as determined by qPCR. Additionally, we observed that CD43 −/− Th17 cells have impaired adhesion to ICAM‐1 in vitro, but express similar levels of LFA‐1, the main ICAM‐1 ligand in T cells, as WT mice. Moreover, WT and CD43 −/− Th17 cells adhered to ICAM‐1 in detachment assays with similar strength. Our results demonstrate the possibility of CD43 interacting with ICAM‐1 to mediate Th17 cell recruitment to sites of inflammation. Future studies will unveil whether direct interaction between CD43 and ICAM‐1 occurs specifically in Th17 cells as a mechanism of Th17 cell recruitment to sites of inflammation independent of E‐sel, such as EAE.