2. Academic Validation
  3. Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis

Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis

  • Nat Commun. 2023 Apr 10;14(1):2004. doi: 10.1038/s41467-023-37798-x.
Xiaojie Cai # 1,  Maoying Han # 2,  Fangzhou Lou 1,  Yang Sun 1,  Qianqian Yin 3,  Libo Sun 1,  Zhikai Wang 3,  Xiangxiao Li 1,  Hong Zhou 1,  Zhenyao Xu 1,  Hong Wang 3,  Siyu Deng 1,  Xichen Zheng 1,  Taiyu Zhang 1,  Qun Li 4,  Bin Zhou 5,  Honglin Wang 6
Affiliations

Affiliations

  • 1 Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 2 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
  • 3 Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 4 The Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 5 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. zhoubin@sibs.ac.cn.
  • 6 Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. honglin.wang@sjtu.edu.cn.
  • # Contributed equally.
PMID: 37037861 DOI: 10.1038/s41467-023-37798-x
Abstract

Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals a Tnc+ papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.

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