Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression
| Autor: | Annemiek B. van Spriel, Mark D. Wright, Frank Alderuccio, Eleanor L. Jones, Louisa Yeung, Michael J. Hickey, Andrew Newman, Hang Fai Kwok, Katrina J. Binger, Zeyad Nasa, Ann Ager, Maria C. Demaria, Rens Peeters, Brodie C. Smith, Janet L. Wee, G. J. Hämmerling, Masa Mihaljcic, Pam Hall |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD53 Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Lymphocyte Immunology 02 engineering and technology Article 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center Immune system Tetraspanin medicine lcsh:Science Immune Response Multidisciplinary biology Chemistry Specialized Functions of Cells 021001 nanoscience & nanotechnology 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein L-selectin Surface expression lcsh:Q Lymph Molecular Mechanism of Behavior 0210 nano-technology Function (biology) |
| Zdroj: | iScience, Vol 23, Iss 5, Pp-(2020) iScience iScience, 23 iScience, 23, 5 |
| ISSN: | 2589-0042 |
| Popis: | Summary 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. Graphical Abstract Highlights • CD53 is essential for lymph node cellularity as Cd53−/− lymph nodes lack T and B cells • CD53 is essential for lymphocyte homing to lymph nodes • CD53 stabilizes L-selectin cell surface expression and may restrain shedding • Impaired lymphocyte homing leads to diminished immune responses in Cd53−/− mice Molecular Mechanism of Behavior; Immunology; Immune Response; Specialized Functions of Cells |
| Databáze: | OpenAIRE |
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