{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:42:34Z","timestamp":1789688554017,"version":"4.0.1"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673095"],"award-info":[{"award-number":["81673095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL\/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4\u2013Dectin2\u2013PLC-\u03b32\u2013NFATC2\u2013Nr4a2\u2013PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.<\/jats:p>","DOI":"10.4049\/jimmunol.2300718","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T09:24:18Z","timestamp":1718011458000},"page":"268-282","source":"Crossref","is-referenced-by-count":9,"title":["CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4\u2013Dectin2\u2013PLC-\u03b32\u2013NFATC2\u2013Nr4a2\u2013PD-L1 Signaling Pathway"],"prefix":"10.1093","volume":"213","author":[{"given":"Benbo","family":"Liu","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"key":"2025012305130048000_r1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.21037\/tlcr-22-108","article-title":"Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review","volume":"11","author":"Yan","year":"2022","journal-title":"Transl. 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