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Tetraspanin CD53 promotes lymphocyte recirculation by stablising L-selectin surface expression

Demaria, Maria C., Yeung, Louisa, Peeters, Rens, Wee, Janet L., Mihaljcic, Masa, Jones, Eleanor L., Nasa, Zeyad, Alderuccio, Frank, Hall, Pamela, Smith, Brodie C., Hammerling, Gunther, Kwok, Hang Fai, Newman, Andrew, Ager, Ann, van Spriel, Annemiek, Hickey, Michael J. and Wright, Mark D. 2020. Tetraspanin CD53 promotes lymphocyte recirculation by stablising L-selectin surface expression. iScience

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Abstract

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyterestricted tetraspanin, CD53 has remained unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53-/- mice were smaller than wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53-/- B cells and reduced stability of L-selectin on Cd53-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 inhibits L-selectin shedding via both ADAM17-dependent and -independent mechanisms. The disruption in lymphocyte recirculation in Cd53-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate a previously unrecognized essential role for CD53 in lymphocyte trafficking and immune responses.

Item Type: Article
Status: In Press
Schools: Medicine
ISSN: 2589-0042
Date of First Compliant Deposit: 28 April 2020
Date of Acceptance: 29 March 2020
Last Modified: 29 Apr 2020 21:56
URI: http://orca-mwe.cf.ac.uk/id/eprint/131234

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