Skip to main content

BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1444777
This article is part of the Research Topic Molecular Characterisation of Autoimmune Diseases View all articles

Humanized CXCL12 Antibody Delays Onset and Modulates Immune Response in Alopecia Areata Mice: Insights from Single-Cell RNA Sequencing

Provisionally accepted
Seungchan An Seungchan An 1Mei Zheng Mei Zheng 2In Guk Park In Guk Park 1Sang Gyu Park Sang Gyu Park 3Minsoo Noh Minsoo Noh 1*Jong-Hyuk Sung Jong-Hyuk Sung 2*
  • 1 Seoul National University, Seoul, Republic of Korea
  • 2 Epi Biotech Co., Ltd, Incheon, Republic of Korea
  • 3 Ajou University, Suweon, Gyeonggi, Republic of Korea

The final, formatted version of the article will be published soon.

    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 Ifng, Cd8a, Ccr5, Ccl4, Ccl5, and Il21r, which were colocalized with Cxcr4 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.

    Keywords: CXCL12, humanized antibody, Alopecia Areata, CD8 + T cell, Interferon-gamma

    Received: 06 Jun 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 An, Zheng, Park, Park, Noh and Sung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Minsoo Noh, Seoul National University, Seoul, 151-742, Republic of Korea
    Jong-Hyuk Sung, Epi Biotech Co., Ltd, Incheon, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.