Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells.

Blood
Anne SchönleRobert Zeiser

Abstract

Caveolin-1 (Cav-1) is a key organizer of membrane specializations and a scaffold protein that regulates signaling in multiple cell types. We found increased Cav-1 expression in human and murine T cells after allogeneic hematopoietic cell transplantation. Indeed, Cav-1(-/-)donor T cells caused less severe acute graft-versus-host disease (GVHD) and yielded higher numbers of regulatory T cells (Tregs) compared with controls. Depletion of Tregs from the graft abrogated this protective effect. Correspondingly, Treg frequencies increased when Cav-1(-/-)T cells were exposed to transforming growth factor-β/T-cell receptor (TCR)/CD28 activation or alloantigen stimulation in vitro compared with wild-type T cells. Mechanistically, we found that the phosphorylation of Cav-1 is dispensable for the control of T-cell fate by using a nonphosphorylatable Cav-1 (Y14F/Y14F) point-mutation variant. Moreover, the close proximity of lymphocyte-specific protein tyrosine kinase (Lck) to the TCR induced by TCR-activation was reduced in Cav-1(-/-)T cells. Therefore, less TCR/Lck clustering results in suboptimal activation of the downstream signaling events, which correlates with the preferential development into a Treg phenotype. Overall, we report a no...Continue Reading

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Citations

Jun 24, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica G BorgerRose Zamoyska
Aug 15, 2017·Nature Immunology·Susana MinguetMiguel A Del Pozo
Sep 20, 2017·Nature Immunology·Julie Zikherman, Clifford A Lowell
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Nov 15, 2018·Frontiers in Cell and Developmental Biology·Noa Beatriz Martín-CófrecesFrancisco Sánchez-Madrid
Oct 11, 2019·The Journal of Biological Chemistry·Su-Ho ParkTae Sung Kim
Nov 8, 2016·Frontiers in Immunology·Petya Apostolova, Robert Zeiser
May 13, 2020·Journal of Cell Science·Albert PolRobert G Parton
Nov 27, 2020·Biochemical Society Transactions·Anna-Maria Schaffer, Susana Minguet
Oct 31, 2020·Pathogens·Bikash Sahay, Ayalew Mergia
Jun 20, 2017·Biomaterials·Bahman DelalatSimon C Barry
May 1, 2021·Cells·Frederike A HartlSusana Minguet
Jun 8, 2021·HemaSphere·Lukas M Braun, Robert Zeiser

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