{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:00:55Z","timestamp":1785477655984,"version":"3.56.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005760","name":"G\u00f6teborgs Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hematopoietic stem cell transplantation (HSCT) after cytotoxic conditioning, such as total-body irradiation (TBI), is widely used to treat hematologic and immune disorders. However, this treatment is associated with long-term systemic effects, including immune and skeletal complications, and the relationship among irradiation, HSCT, and subsequent inflammatory responses remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the long-term effects of TBI and HSCT on immune and skeletal responses, antigen-induced arthritis (AIA) was induced as a localized inflammatory challenge either 2 weeks (early) or 10 weeks (late) after transplantation. Clinical, immunological, and skeletal outcomes were assessed, including arthritis severity, body weight, immune cell composition, bone morphology, bone turnover markers, and antibody responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TBI and HSCT did not alter the severity of antigen-induced arthritis. However, transplanted mice showed greater systemic vulnerability following immune challenge, with reduced body weight, organ atrophy, and increased bone marrow apoptosis, indicating prolonged systemic stress. Bone analyses revealed persistent bone loss after TBI and HSCT, with greater trabecular bone loss in the arthritic limb and elevated serum CTX-1 levels, reflecting enhanced osteoclast-mediated bone resorption. Immune responses also changed over time, with early granulocyte expansion followed by delayed lymphocyte recovery, both associated with increased circulating TGF-\u03b21 levels. In addition, antigen-specific IgG responses were reduced following late immune activation in both na\u00efve and irradiated-transplanted mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TBI followed by HSCT induces systemic vulnerability, immune dysregulation, and skeletal deterioration that persists beyond hematopoietic recovery. Although local arthritis severity is unaffected, the host exhibits heightened susceptibility to systemic stress and bone loss after inflammatory challenge, highlighting the long.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1890654","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:38:44Z","timestamp":1785476324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-dependent immune and skeletal alterations following total-body irradiation and hematopoietic stem cell transplantation in a murine arthritis model"],"prefix":"10.3389","volume":"17","author":[{"given":"Priti","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg","place":["Gothenburg, Sweden"]},{"name":"Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis 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