{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:00:16Z","timestamp":1785376816712,"version":"3.55.0"},"posted":{"date-parts":[[2025,2,21]]},"group-title":"Molecular Biology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A transplanted lung offers a permissive\n                  <jats:italic>milieu<\/jats:italic>\n                  for local adaptive immune cell responses. Here, we characterize a transcriptionally and anatomically distinct adult lung-resident mesenchymal stromal population (MSC) that supports a pro-survival niche for antibody-secreting cells in rejecting lung allografts through a novel IL-6 trans-signaling\/CXCL12 axis. By using a mouse orthotopic lung transplant model and\n                  <jats:italic>\n                    Blimp1\n                    <jats:sup>EYFP<\/jats:sup>\n                  <\/jats:italic>\n                  recipients, we identify spatial localization of antibody-secreting cells (ASCs) and terminally differentiated plasma cells (PCs) along the bronchovascular bundles (BVBs). A previously described Foxf1\n                  <jats:sup>+<\/jats:sup>\n                  Gli1\n                  <jats:sup>+<\/jats:sup>\n                  Itga8\n                  <jats:sup>\u2212<\/jats:sup>\n                  subset of collagen- expressing MSCs, which forms a 3-dimensional network along the bronchovascular bundles (BVB-MSCs), was found to be the major source of the PC survival factors CXCL12 and IL-6.\n                  <jats:italic>\n                    Cxcl12\n                    <jats:sup>iCre\/ERT2<\/jats:sup>\n                    Rosa26\n                    <jats:sup>tdTomato<\/jats:sup>\n                  <\/jats:italic>\n                  mice utilized as donors, validated the expansion of this population in a rejecting graft and their intimate association with ASCs. CXCL12 expression was increased in murine allografts and in Foxf1\n                  <jats:sup>+<\/jats:sup>\n                  mesenchymal cells (MCs) isolated from human CLAD patients. IL-6 trans-signaling\/STAT3 signaling axis was shown to upregulate CXCL12 secretion in human MCs, and Olamkicept-mediated neutralization of IL-6 trans-signaling in murine RAS attenuates CXCL12 expression, intra-graft ASC population, and fibrogenesis. Our findings represent the first delineation of specialized CXCL12-expressing mesenchymal stromal cells in adult lungs and the contribution of IL-6 trans-signaling driven CXCL12 expression to sustaining intra-graft ASC niches and allograft fibrogenesis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>We characterize CXCL12-expressing mesenchymal cells and their role in a pro-survival niche for antibody-secreting cells in rejecting lung allografts.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.16.638532","type":"posted-content","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T05:20:23Z","timestamp":1740115223000},"source":"Crossref","is-referenced-by-count":3,"title":["IL-6 trans-signaling regulates CXCL12 expression in mesenchymal stromal cells and plasma cell niche in rejecting lung allografts"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-5314","authenticated-orcid":false,"given":"A. 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