Effector and Regulatory T Cells Roll at High Shear Stress by Inducible Tether and Sling Formation

Autor: Michael Abadier, Akula Bala Pramod, Sara McArdle, Alex Marki, Zhichao Fan, Edgar Gutierrez, Alex Groisman, Klaus Ley
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 21, Iss 13, Pp 3885-3899 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.11.099
Popis: The adaptive immune response involves T cell differentiation and migration to sites of inflammation. T cell trafficking is initiated by rolling on inflamed endothelium. Tethers and slings, discovered in neutrophils, facilitate cell rolling at high shear stress. Here, we demonstrate that the ability to form tethers and slings during rolling is highly inducible in T helper 1 (Th1), Th17, and regulatory T (Treg) cells but less in Th2 cells. In vivo, endogenous Treg cells rolled stably in cremaster venules at physiological shear stress. Quantitative dynamic footprinting nanoscopy of Th1, Th17, and Treg cells uncovered the formation of multiple tethers per cell. Human Th1 cells also showed tethers and slings. RNA sequencing (RNA-seq) revealed the induction of cell migration and cytoskeletal genes in sling-forming cells. We conclude that differentiated CD4 T cells stabilize rolling by inducible tether and sling formation. These phenotypic changes approximate the adhesion phenotype of neutrophils and support CD4 T cell access to sites of inflammation.
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