{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:17:54Z","timestamp":1793726274946,"version":"4.6.1"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Lymphotoxin beta receptor (LT\u03b2R) is a promising therapeutic target in autoimmune and infectious diseases as well as cancer. Mice with genetic inactivation of LT\u03b2R display multiple defects in development and organization of lymphoid organs, mucosal immune responses, IgA production and an autoimmune phenotype. As these defects are imprinted in embryogenesis and neonate stages, the impact of LT\u03b2R signaling in adulthood remains unclear. Here, to overcome developmental defects, we generated mice with inducible ubiquitous genetic inactivation of LT\u03b2R in adult mice (iLT\u03b2R<jats:sup>\u0394\/\u0394<\/jats:sup> mice) and redefined the role of LT\u03b2R signaling in organization of lymphoid organs, immune response to mucosal bacterial pathogen, IgA production and autoimmunity. In spleen, postnatal LT\u03b2R signaling is required for development of B cell follicles, follicular dendritic cells (FDCs), recruitment of neutrophils and maintenance of the marginal zone. Lymph nodes of iLT\u03b2R<jats:sup>\u0394\/\u0394<\/jats:sup> mice were reduced in size, lacked FDCs, and had disorganized subcapsular sinus macrophages. Peyer`s patches were smaller in size and numbers, and displayed reduced FDCs. The number of isolated lymphoid follicles in small intestine and colon were also reduced. In contrast to LT\u03b2R<jats:sup>-\/-<\/jats:sup> mice, iLT\u03b2R<jats:sup>\u0394\/\u0394<\/jats:sup> mice displayed normal thymus structure and did not develop signs of systemic inflammation and autoimmunity. Further, our results suggest that LT\u03b2R signaling in adulthood is required for homeostasis of neutrophils, NK, and iNKT cells, but is dispensable for the maintenance of polyclonal IgA production. However, iLT\u03b2R<jats:sup>\u0394\/\u0394<\/jats:sup> mice exhibited an increased sensitivity to <jats:italic>C. rodentium<\/jats:italic> infection and failed to develop pathogen-specific IgA responses. Collectively, our study uncovers new insights of LT\u03b2R signaling in adulthood for the maintenance of lymphoid organs, neutrophils, NK and iNKT cells, and IgA production in response to mucosal bacterial pathogen.<\/jats:p>","DOI":"10.3389\/fimmu.2021.712632","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T18:18:27Z","timestamp":1626373107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["Redefining the Role of Lymphotoxin Beta Receptor in the Maintenance of Lymphoid Organs and Immune Cell Homeostasis in Adulthood"],"prefix":"10.3389","volume":"12","author":[{"given":"Yajun","family":"Shou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Koroleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody 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