{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T03:40:46Z","timestamp":1775014846567,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"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:p>Blockade of PD-1, an indispensable physiological immunoregulatory mechanism, enhances immune activities and is widely used in the immunotherapy of cancer. This treatment often accompanies inflammatory complication called immune-related adverse events (irAE), most frequently in the skin. To analyze how skin inflammation develops by the blockade of PD-1-dependent immunoregulation, we studied the exacerbation of oxazolone-induced contact hypersensitivity by PD-L1 blockade. The inactivation of PD-1 signaling enhanced swelling of the skin with massive CD8<jats:sup>+<\/jats:sup>T cell infiltration. Among PD-1-expressing cells, T cells were the predominant targets of anti-PD-L1 mAb treatment since PD-L1 blockade did not affect skin inflammation in RAG2<jats:sup>-\/-<\/jats:sup>mice. PD-L1 blockade during immunization with oxazolone significantly promoted the development of hapten-reactive T cells in the draining lymph nodes. The enhancement of local CD8<jats:sup>+<\/jats:sup>T cell-dominant immune responses by PD-L1 blockade was correlated with the upregulation of CXCL9 and CXCL10. Challenges with a low dose of oxazolone did not demonstrate any significant dermatitis; however, the influence of PD-L1 blockade on T cell immunity was strong enough to cause the emergence of notable dermatitis in this suboptimal dosing, suggesting its relevance to dermal irAE development. In the low-dose setting, the blockade of CXCR3, receptor of CXCL9\/10, prevented the induction of T cell-dominant inflammation by anti-PD-L1 mAb. This experimental approach reproduced CD8<jats:sup>+<\/jats:sup>T cell-dominant form of cutaneous inflammation by the blockade of PD-L1 that has been observed in dermal irAE in human patients.<\/jats:p>","DOI":"10.3389\/fimmu.2020.618711","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T07:04:38Z","timestamp":1611731078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Inactivation of the PD-1-Dependent Immunoregulation in Mice Exacerbates Contact Hypersensitivity Resembling Immune-Related Adverse Events"],"prefix":"10.3389","volume":"11","author":[{"given":"Matin 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