Tetraspanin CD53 promotes lymphocyte recirculation by stabilizing L-selectin surface expression
journal contribution
posted on 2025-10-15, 06:22 authored by Maria C. Demaria, L Yeung, R Peeters, JL Wee, M Mihaljcic, EL Jones, Z Nasa, F Alderuccio, P Hall, BC Smith, Katrina BingerKatrina Binger, G Hammerling, HF Kwok, A Newman, A Ager, A van Spriel, MJ Hickey, MD Wright<p dir="ltr">Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of 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 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-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 an essential role for CD53 in lymphocyte trafficking and immunity.</p>
