{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:31:08Z","timestamp":1792171868306,"version":"4.4.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"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>It has been demonstrated that CXCL12 inhibits hair growth via CXCR4, and its neutralizing antibody (Ab) increases hair growth in alopecia areata (AA). However, the molecular mechanisms have not been fully elucidated. In the present study, we further prepared humanized CXCL12 Ab for AA treatment and investigated underlying molecular mechanisms using single-cell RNA sequencing. Subcutaneous injection of humanized CXCL12 Ab significantly delayed AA onset in mice, and dorsal skin was analyzed. T cells and dendritic cells\/macrophages were increased in the AA model, but decreased after CXCL12 Ab treatment. Pseudobulk RNA sequencing identified 153 differentially expressed genes that were upregulated in AA model and downregulated after Ab treatment. Gene ontology analysis revealed that immune cell chemotaxis and cellular response to type II interferon were upregulated in AA model but downregulated after Ab treatment. We further identified key immune cell-related genes such as <jats:italic>Ifng<\/jats:italic>, <jats:italic>Cd8a<\/jats:italic>, <jats:italic>Ccr5<\/jats:italic>, <jats:italic>Ccl4<\/jats:italic>, <jats:italic>Ccl5<\/jats:italic>, and <jats:italic>Il21r<\/jats:italic>, which were colocalized with <jats:italic>Cxcr4<\/jats:italic> in T cells and regulated by CXCL12 Ab treatment. Notably, CD8+ T cells were significantly increased and activated via Jak\/Stat pathway in the AA model but inactivated after CXCL12 Ab treatment. Collectively, these results indicate that humanized CXCL12 Ab is promising for AA treatment via immune modulatory effects.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1444777","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:39:42Z","timestamp":1729139982000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Humanized CXCL12 antibody delays onset and modulates immune response in alopecia areata mice: insights from single-cell RNA sequencing"],"prefix":"10.3389","volume":"15","author":[{"given":"Seungchan","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Guk","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Gyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsoo","family":"Noh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyuk","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.cytogfr.2018.10.004","article-title":"Pathological roles of the homeostatic chemokine CXCL12","volume":"44","author":"Janssens","year":"2018","journal-title":"Cytokine Growth Factor Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/med.22011","article-title":"CXCR4\/CXCL12 axis: \u201cold\u201d pathway as \u201cnovel\u201d target for anti-inflammatory drug discovery","volume":"44","author":"Lu","year":"2024","journal-title":"Med Res Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909602","article-title":"The multiple faces of CXCL12 (SDF-1alpha) in the regulation of immunity during health and disease","volume":"88","author":"Karin","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00974-6","article-title":"The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention","volume":"20","author":"Cambier","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00585","article-title":"The role of the CXCL12\/CXCR4\/ACKR3 axis in autoimmune diseases","volume":"10","author":"Garcia-Cuesta","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20231425","article-title":"CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17","volume":"221","author":"Cavagnero","year":"2024","journal-title":"J Exp Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.37349\/ei","article-title":"Macrophages and fibroblasts underpin skin immune responses. 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