The beta2 integrin-kindlin-3 interaction is essential for T-cell homing but dispensable for T-cell activation in vivo

Morrison, V.L., MacPherson, M., Savinko, T., San Lek, H., Prescott, A. and Fagerholm, S.C. (2013) The beta2 integrin-kindlin-3 interaction is essential for T-cell homing but dispensable for T-cell activation in vivo. Blood, 122(8), pp. 1428-1436. (doi:10.1182/blood-2013-02-484998) (PMID:23823319) (PMCID:PMC3750339)

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Abstract

Kindlin-3 is mutated in the rare genetic disorder, Leukocyte Adhesion Deficiency type-III, which is characterized by deficient integrin-mediated adhesion of leukocytes and platelets. However, the specific roles of kindlin-3-beta2-integrin interactions in T cell adhesion, homing and immune responses in vivo remain unclear. Here, we show that the TTT-motif in beta2 integrins controls kindlin-3 binding. Mutation of the kindlin-3 binding site in beta2 integrins caused a loss of firm adhesion of T cells under both static and shear flow conditions and a reduction of T cell homing to lymph nodes in vivo. However, atomic force microscopy studies of integrin-ligand bonds revealed that initial ligand binding could still occur, and 2D T cell migration was reduced but not abolished by the TTT/AAA mutation in the beta2 integrin. Importantly, DC-mediated T cell activation in vivo was normal in TTT/AAA beta2 integrin knock-in mice. Our results reveal a selective role of the kindlin-3–integrin association for lymphocyte functions in vivo; the integrin-kindlin-3 interaction is particularly important in adhesion strengthening under shear flow, and for T cell homing to lymph nodes, but dispensable for T cell activation which occurs in a shear-free environment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morrison, Dr Vicky
Authors: Morrison, V.L., MacPherson, M., Savinko, T., San Lek, H., Prescott, A., and Fagerholm, S.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020

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