Inflammation-induced Interstitial Migration of Effector CD4⁺ T Cells Is Dependent on Integrin αV

Nat Immunol. 2013 Sep;14(9):949-58. doi: 10.1038/ni.2682. Epub 2013 Aug 11.

Abstract

Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues seems to be integrin independent and based on actomyosin-mediated protrusion and contraction, during inflammation, changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that the interstitial motility of T cells was critically dependent on Arg-Gly-Asp (RGD)-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to higher expression of integrin αV on effector CD4⁺ T cells. By intravital multiphoton imaging, we found that the motility of CD4⁺ T cells was dependent on αV expression. Selective blockade or knockdown of αV arrested T helper type 1 (TH1) cells in the inflamed tissue and attenuated local effector function. Our data demonstrate context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Movement / immunology*
  • Dermis / immunology
  • Dermis / metabolism
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Integrin alphaV / genetics
  • Integrin alphaV / metabolism*
  • Lymph Nodes / immunology
  • Mice
  • Oligopeptides / metabolism
  • Protein Binding
  • Th1 Cells / immunology
  • Th1 Cells / metabolism

Substances

  • Integrin alphaV
  • Oligopeptides
  • arginyl-glycyl-aspartic acid