{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:24:42Z","timestamp":1788546282614,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Human Dental Pulp Stromal Cells (hDPSCs) of neural-ectodermal origin hold immunomodulatory properties which make them a source for MSC-based therapies for the treatment of autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study hDPSCs were exposed to inflammatory conditions mimicked by co-culture with Peripheral Blood Mononuclear Cells activated with anti-CD3\/CD28 (aPBMCs) or treatment with Conditioned Medium (CM) from aPBMCs with or without the addition of a specific IL6 receptor (IL6R) inhibitor. To assess IL-6 effects on PD-L1 expression, hDPSCs were treated with IL-6\/sIL6R complex and the activation of IL-6 trans-signalling was investigated. The functional role of IL-6 in modulating PD-L1 protein stability was further confirmed by treating hDPSCs with a proteasome inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results highlighted that hDPSCs exposed to different inflammatory conditions activate Fas\/FasL and PD1\/PD-L1 pathways. Moreover, hDPSCs modulate inflammatory cytokines release of aPBMCs from Rheumatoid Arthritis (RA) patients. However, the inflammatory milieu induced the upregulation of IL-6 by hDPSCs, which was demonstrated to be strongly correlated to PD-L1 expression, suggesting its involvement in supporting their immunoregulation. Our data demonstrated that the activation of the IL6\/JAK\/STAT3 trans-signaling pathway in hDPSCs through stimulation with the IL6\/sIL6R complex leads to an increase in PD-L1 protein levels, but not PD-L2, via proteasome inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates the activation of the IL-6\/PD-L1 axis in response to inflammatory conditions and underscores its potential significance in autoimmune diseases since a dysfunction of this mechanism could lead to the onset and progression of chronic inflammatory disorders.<\/jats:p>\n                  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