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Contribution of E‐selectin Ligands and the Chemokine CCL20 to Th17 Lymphocyte Rolling and Transendothelial Migration
Author(s) -
GrodeckiPena Anna,
Knapp Andrew,
Salvador Ane Miren,
Alcaide Pilar
Publication year - 2013
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.27.1_supplement.57.6
Subject(s) - cd43 , ccl20 , cd44 , microbiology and biotechnology , chemokine , chemistry , c c chemokine receptor type 6 , flow cytometry , cell , inflammation , biology , immunology , chemokine receptor , biochemistry , antibody , cd20
IL17 producing T helper lymphocytes (Th17 cells) are often recruited at sites of tissue inflammation. This requires interactions with the vascular endothelium, and these interactions are quantitatively different from other T cell subsets (e.g, Th1 cells) and highly dependent on E‐selectin, ICAM‐1 and the chemokine CCL20. CD44 and CD43 cooperate with PSGL‐1 to mediate Th1 cells E‐selectin rolling, but their role in Th17 cells is unclear. Similarly, the role of CCL20 in Th17 cell transendothelial migration (TEM) has not been explored. We examined the contribution of the E‐selectin ligands PSGL‐1, CD44 and CD43 to Th17 cell adhesion to E‐selectin using wild type (WT), CD44 −/− /PSGL‐1 −/− and CD43 −/− /PSGL1 −/− deficient mice. Flow cytometry revealed that Th17 cells expressed all three ligands, with CD44 and PSGL‐1 at levels comparable to Th1 cells, and CD43 at significantly higher levels. Very few CD43 −/− /PSGL1 −/− Th17 cells accumulated on E‐selectin under shear flow conditions compared with WT or CD44 −/− /PSGL‐1 −/− cells. Blot rolling studies on Th17 lysates revealed a main reactive E‐selectin rolling area corresponding to CD43. Using WT and ICAM‐1 −/− endothelial cells, we also examined the ability of CCL20 to induce Th17 cell TEM and whether this was dependent on ICAM‐1. Our data shows that Th17 cell rolling on E‐selectin is mainly mediated by CD43 whereas Th17 cell TEM requires CCL20 and ICAM‐1. NIH K99‐HL097406.