{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:33:00Z","timestamp":1784633580150,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R56AR078279\u201001A1"],"award-info":[{"award-number":["1R56AR078279\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI134030"],"award-info":[{"award-number":["R01AI134030"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03HL15863"],"award-info":[{"award-number":["R03HL15863"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Patients with systemic lupus erythematosus (SLE) experience photosensitivity, with exposure to UVB light driving lupus flares and triggering symptoms like joint pain, fatigue, and cutaneous lesions. Although the mechanism(s) linking UVB exposure to systemic effects are unclear, type I interferons (IFNs) are known to play a role. Our previous work has shown that TRIM21, an autoantigen in SLE, functions as a negative regulator on the pathways driving IFN expression. Here we explore how TRIM21 functions to regulate both local and systemic inflammation following UVB exposure and how altered expression may drive cutaneous inflammation and photosensitivity in SLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type (WT; C57BL\/6) and\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice were irradiated with UVB (100 mJ\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) on the shaved dorsal region on consecutive days for 1 and 3 weeks, and UVB\u2010induced local cutaneous manifestations and systemic inflammation in blood, spleen, and kidney were examined by messenger RNA expression of inflammatory and type I IFN response genes, histology, and flow cytometry. Mechanistic studies were performed in bone marrow\u2013derived macrophages (BMDMs) and murine dermal fibroblasts (MDFs) from WT and\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice and\n                      <jats:italic>TRIM21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      THP\u20101 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Infiltration of inflammatory cells and induction of type I IFN developed in UVB\u2010exposed areas in both sets of mice. Most notably after UVB exposure, we observed splenomegaly and enhanced expression of IFN\u2010stimulated genes in the blood and spleen of\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Inflammatory chemokines CXCL10 and CXCL12 were also detected at significantly higher levels in serum of\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice after UVB exposure.\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice exposed to UVB also demonstrated enhanced total IgG levels in serum accompanied by increased skin and kidney deposition of IgG and increased glomerular cellularity and size. To determine the mechanism, we assessed UVB\u2010 and cyclic GMP\u2010AMP\u2013dependent\n                      <jats:italic>Ifnb1<\/jats:italic>\n                      expression in\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      BMDMs and MDFs, noting increased responses compared with WT cells. This effect was lost in BMDMs from\n                      <jats:italic>Trim21\/Sting1<\/jats:italic>\n                      double knockout mice and skin explants, in keeping with the ability of TRIM21 to regulate cytoplasmic DNA sensing. In keeping with previous reports, we found that degradation of both DDX41 and STING levels were affected in stimulated\n                      <jats:italic>Trim21<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      BMDMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, our results indicate that TRIM21 protects against IFN induction at both local and systemic levels by restricting STING signaling.<\/jats:p>\n                  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