{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:56:39Z","timestamp":1792443399329,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1108800"],"award-info":[{"award-number":["1108800"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI100627"],"award-info":[{"award-number":["U19 AI100627"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1081858"],"award-info":[{"award-number":["1081858"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Inherited mutations in lipopolysaccharide\u2010responsive beige\u2010like anchor (<jats:italic>LRBA<\/jats:italic>) cause a recessive human immune dysregulation syndrome with memory B\u2010cell and antibody deficiency (common variable immunodeficiency), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL\/6 mice carrying a homozygous truncating mutation in <jats:italic>Lrba<\/jats:italic> were produced using CRISPR\/Cas9\u2010mediated gene targeting. These mice revealed that LRBA has a critical, cell\u2010autonomous role in promoting cytotoxic T\u2010lymphocyte antigen\u20104 (CTLA\u20104) accumulation within CD4 effector T cells and FOXP3<jats:sup>+<\/jats:sup> T\u2010regulatory cells (Tregs). In young mice, or in chimeric mice where only half of the T cells are LRBA deficient, low CTLA\u20104 was the only detectable abnormality in Tregs, whereas in old mice FOXP3 was also decreased. Low CTLA\u20104 did not translate into increased CD86 on B cells unless the LRBA\u2010deficient mice were immunised, and neither immunisation nor chronic lymphocytic choriomeningitis virus infection precipitated immune dysregulation. LRBA deficiency did not alter antigen\u2010specific B\u2010cell activation, germinal centre (GC) formation, isotype switching or affinity maturation. Paradoxically, CD86 was decreased on GC B cells in LRBA\u2010deficient mice, pointing to compensatory mechanisms for controlling CD86 in the face of low CTLA\u20104. These results add to the experimental rationale for treating LRBA deficiency with the CTLA4\u2010Ig fusion protein, Abatacept, and pose questions about the limitations of laboratory experiments in mice to reproduce human disease <jats:italic>in natura<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/icb.2017.50","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T08:21:01Z","timestamp":1497428461000},"page":"775-788","source":"Crossref","is-referenced-by-count":41,"title":["Murine LRBA deficiency causes CTLA\u20104 deficiency in Tregs without progression to immune dysregulation"],"prefix":"10.1111","volume":"95","author":[{"given":"Deborah L","family":"Burnett","sequence":"first","affiliation":[{"name":"Immunology Division, Garvan Institute for Medical Research  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A","family":"Parish","sequence":"additional","affiliation":[{"name":"John Curtin School of Medical Research, Australian National University  Canberra ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Masle\u2010Farquhar","sequence":"additional","affiliation":[{"name":"Immunology Division, Garvan Institute for Medical Research  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brink","sequence":"additional","affiliation":[{"name":"Immunology Division, Garvan Institute for Medical Research  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C","family":"Goodnow","sequence":"additional","affiliation":[{"name":"Immunology Division, Garvan Institute for Medical Research  Sydney NSW 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