Cd53, also known as Tetraspanin 25 (TSPAN25) and MOX44, is a member of the tetraspanin superfamily. Tetraspanins are membrane-organizing proteins that form subcellular domains, and Cd53 is expressed exclusively within the immune compartment. It plays vital roles in immune cell function, lymphocyte trafficking, and cell-cycle regulation in hematopoietic stem cells (HSCs), and is also involved in the regulation of lipid metabolism and inflammation in hepatocytes [1,4,6,7].

In gene-knockout mouse models, Cd53-deficient (Cd53-/-) mice show multiple phenotypes. In lymphocytes, Cd53-/-B and T cells have reduced ability to home to lymph nodes due to decreased L-selectin expression or stability, leading to smaller lymph nodes and impaired immune responses [4]. Cd53-/-T cells exhibit proliferation defects, and Cd53-/-mice show impaired tumor rejection and reduced IFNγ-producing T cells, as Cd53 is required for CD45RO expression, mobility, and optimal phosphatase activity [2]. In early B-cell development, Cd53-/-mice have decreased B-cell populations, as Cd53 promotes IL-7R signaling [5]. In hepatocytes, germline Cd53 deletion blocks Western diet-induced dyslipidemia and hepatic inflammatory transcriptomic activation [6]. In HSCs, loss of Cd53 is associated with prolonged cycling and reduced function during inflammatory stress, as Cd53 promotes DREAM complex-mediated quiescence [7]. In neutrophils, Cd53-/-mice have reduced neutrophil recruitment to the inflamed peritoneal cavity and defects in transmigration, cytoskeletal remodeling, and integrin regulation [8].

In conclusion, Cd53 is essential for various biological processes. Its role in immune cell function, lymphocyte trafficking, and HSC quiescence is well-demonstrated through gene-knockout mouse models. These models also highlight its potential implications in diseases related to immune dysfunction, such as recurrent infections, autoimmunity, and tumor immunity, as well as metabolic diseases like non-alcoholic steatohepatitis [1,3,6].

References:

1. Dunlock, V E. 2020. Tetraspanin CD53: an overlooked regulator of immune cell function. In Medical microbiology and immunology, 209, 545-552. doi:10.1007/s00430-020-00677-z. https://pubmed.ncbi.nlm.nih.gov/32440787/

2. Dunlock, Vera-Marie E, Arp, Abbey B, Singh, Simar Pal, Rubinstein, Eric, van Spriel, Annemiek B. . Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function. In Cell reports, 39, 111006. doi:10.1016/j.celrep.2022.111006. https://pubmed.ncbi.nlm.nih.gov/35767951/

3. Yeung, Louisa, Gottschalk, Timothy A, Hall, Pam, Wright, Mark D, Hickey, Michael J. 2021. Tetraspanin CD53 modulates lymphocyte trafficking but not systemic autoimmunity in Lyn-deficient mice. In Immunology and cell biology, 99, 1053-1066. doi:10.1111/imcb.12501. https://pubmed.ncbi.nlm.nih.gov/34514627/

4. Demaria, Maria C, Yeung, Louisa, Peeters, Rens, Hickey, Michael J, Wright, Mark D. 2020. Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression. In iScience, 23, 101104. doi:10.1016/j.isci.2020.101104. https://pubmed.ncbi.nlm.nih.gov/32428859/

5. Greenberg, Zev J, Monlish, Darlene A, Bartnett, Rachel L, Bednarski, Jeffrey J, Schuettpelz, Laura G. 2019. The Tetraspanin CD53 Regulates Early B Cell Development by Promoting IL-7R Signaling. In Journal of immunology (Baltimore, Md. : 1950), 204, 58-67. doi:10.4049/jimmunol.1900539. https://pubmed.ncbi.nlm.nih.gov/31748347/

6. Higgins, Cassandra B, Adams, Joshua A, Ward, Matthew H, Schuettpelz, Laura G, DeBosch, Brian J. 2022. The tetraspanin transmembrane protein CD53 mediates dyslipidemia and integrates inflammatory and metabolic signaling in hepatocytes. In The Journal of biological chemistry, 299, 102835. doi:10.1016/j.jbc.2022.102835. https://pubmed.ncbi.nlm.nih.gov/36581203/

7. Greenberg, Zev J, Paracatu, Luana Chiquetto, Monlish, Darlene A, Luke, Cliff J, Schuettpelz, Laura G. . The tetraspanin CD53 protects stressed hematopoietic stem cells via promotion of DREAM complex-mediated quiescence. In Blood, 141, 1180-1193. doi:10.1182/blood.2022016929. https://pubmed.ncbi.nlm.nih.gov/36542833/

8. Yeung, Louisa, Anderson, Jeremy M L, Wee, Janet L, Wright, Mark D, Hickey, Michael J. 2020. Leukocyte Tetraspanin CD53 Restrains α3 Integrin Mobilization and Facilitates Cytoskeletal Remodeling and Transmigration in Mice. In Journal of immunology (Baltimore, Md. : 1950), 205, 521-532. doi:10.4049/jimmunol.1901054. https://pubmed.ncbi.nlm.nih.gov/32532837/