Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction During Intranodal Migration of T Cells

Nat Immunol. 2018 Jun;19(6):606-616. doi: 10.1038/s41590-018-0109-z. Epub 2018 May 18.

Abstract

Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / immunology*
  • Actins / metabolism
  • Animals
  • Chemokines / immunology
  • Chemokines / metabolism
  • Chemotaxis, Leukocyte / immunology*
  • Friction
  • Integrins / immunology
  • Integrins / metabolism
  • Lymph Nodes
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CCR7 / immunology*
  • Receptors, CCR7 / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Actins
  • Ccr7 protein, mouse
  • Chemokines
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, CCR7