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ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells.

Abstract：

:L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naïve and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation in vitro which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Mohammed RN,Wehenkel SC,Galkina EV,Yates EK,Preece G,Newman A,Watson HA,Ohme J,Bridgeman JS,Durairaj RRP,Moon OR,Ladell K,Miners KL,Dolton G,Troeberg L,Kashiwagi M,Murphy G,Nagase H,Price DA,Matthews RJ,Knäuper V

doi

10.1038/s41598-019-41811-z

subject

Has Abstract

pub_date

2019-04-02 00:00:00

pages

5487

issue

1

issn

2045-2322

pii

10.1038/s41598-019-41811-z

journal_volume

9

pub_type

杂志文章

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