{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:52:32Z","timestamp":1785232352684,"version":"3.55.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Splenic long-lived plasma cells are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b<jats:sup>+<\/jats:sup>Gr-1<jats:sup>+<\/jats:sup>myeloid cells (SDMCs) underpins the accumulation of splenic long-lived plasma cells in a lupus-prone model named sanroque. We found that SDMCs were progressively accumulated in sanroque mice from the early clinical phase. Transcriptome profiles revealed that SDMCs have a predominant shift toward an inflammatory phenotype relative to the bone marrow-derived counterparts and are distinct from neutrophils and monocytes. SDMCs were expanded<jats:italic>in situ<\/jats:italic>via splenic extramedullary myelopoiesis under the proinflammatory cytokine milieu during lupus progression. SDMCs promoted the development of IFN-\u03b3-secreting Th1 and follicular helper T cells, thereby licensing CD4<jats:sup>+<\/jats:sup>T cells to be pathologic activators of SDMCs and plasma cells. SDMCs also directly promoted the survival of plasma cells by providing B-cell activating factor of the TNF family. The frequency of SDMCs correlated with that of splenic long-lived plasma cells. Selective depletion of CD11b<jats:sup>+<\/jats:sup>Gr-1<jats:sup>+<\/jats:sup>cells reduced autoantibody production in sanroque mice. Thus, our findings suggest that SDMCs expanded<jats:italic>in situ<\/jats:italic>establish a positive feedback loop with CD4<jats:sup>+<\/jats:sup>T cells, leading to accumulation of long-lived plasma cells which exacerbates lupus autoimmunity.<\/jats:p>","DOI":"10.3389\/fimmu.2021.631472","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T21:12:01Z","timestamp":1613164321000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus 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