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Fibroblast: A Novel Target for Autoimmune and Inflammatory Skin Diseases Therapeutics

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Abstract

Fibroblasts are crucial components of the skin structure. They were traditionally believed to maintain the skin’s structure by producing extracellular matrix and other elements. Recent research illuminated that fibroblasts can respond to external stimuli and exhibit diverse functions, such as the secretion of pro-inflammatory factors, adipogenesis, and antigen presentation, exhibiting remarkable heterogeneity and plasticity. This revelation positions fibroblasts as active contributors to the pathogenesis of skin diseases, challenging the traditional perspective that views fibroblasts solely as structural entities. Based on their diverse functions, fibroblasts can be categorized into six subtypes: pro-inflammatory fibroblasts, myofibroblasts, adipogenic fibroblasts, angiogenic fibroblasts, mesenchymal fibroblasts, and antigen-presenting fibroblasts. Cytokines, metabolism, and epigenetics regulate functional abnormalities in fibroblasts. The dynamic changes fibroblasts exhibit in different diseases and disease states warrant a comprehensive discussion. We focus on dermal fibroblasts’ aberrant manifestations and pivotal roles in inflammatory and autoimmune skin diseases, including psoriasis, vitiligo, lupus erythematosus, scleroderma, and atopic dermatitis, and propose targeting aberrantly activated fibroblasts as a potential therapeutic strategy for inflammatory and autoimmune skin diseases.

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Funding

This work was supported by the National Key R&D Program of China (2022YFC3601800), the National Natural Science Foundation of China (No. 82030097 and No. 32141004), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2022-RC310-04), and the CAMS Innovation Fund for Medical Sciences (CIFMS) No.2021-I2M-1-059.

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  1. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second **angya Hospital, Central South University, Changsha, 410011, China

    **aoyun Chen, Yutong Wu & Ming Zhao

  2. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nan**g, 210042, China

    Sujie Jia & Ming Zhao

  3. Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nan**g, China

    Sujie Jia & Ming Zhao

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**aoyun Chen wrote and revised the manuscript. Yutong Wu revised the manuscript. SuJie Jia and Ming Zhao provided crucial advice and revised the manuscript. All authors read and approved the final paper.

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Chen, X., Wu, Y., Jia, S. et al. Fibroblast: A Novel Target for Autoimmune and Inflammatory Skin Diseases Therapeutics. Clinic Rev Allerg Immunol (2024). https://doi.org/10.1007/s12016-024-08997-1

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