Inflammation-induced interstitial migration of effector CD4⁺ T cells is dependent on integrin αV.
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.
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, New York, USA.
Michael G
MG
Overstreet
Alison
A
Gaylo
Bastian R
BR
Angermann
Angela
A
Hughson
Young-Min
YM
Hyun
Kris
K
Lambert
Mridu
M
Acharya
Alison C
AC
Billroth-Maclurg
Alexander F
AF
Rosenberg
David J
DJ
Topham
Hideo
H
Yagita
Minsoo
M
Kim
Adam
A
Lacy-Hulbert
Martin
M
Meier-Schellersheim
Deborah J
DJ
Fowell
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D020405:Dermis / Q000276:immunology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D039564:Integrin alphaV; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid