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

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.

Chen X ，Wu Y ，Jia S ，Zhao M ... -  《-》

The role of dermal fibroblasts in autoimmune skin diseases.

Fibroblasts are an important subset of mesenchymal cells in maintaining skin homeostasis and resisting harmful stimuli. Meanwhile, fibroblasts modulate immune cell function by secreting cytokines, thereby implicating their involvement in various dermatological conditions such as psoriasis, vitiligo, and atopic dermatitis. Recently, variations in the subtypes of fibroblasts and their expression profiles have been identified in these prevalent autoimmune skin diseases, implying that fibroblasts may exhibit distinct functionalities across different diseases. In this review, from the perspective of their fundamental functions and remarkable heterogeneity, we have comprehensively collected evidence on the role of fibroblasts and their distinct subpopulations in psoriasis, vitiligo, atopic dermatitis, and scleroderma. Importantly, these findings hold promise for guiding future research directions and identifying novel therapeutic targets for treating these diseases.

Shi Z ，Liu Z ，Wei Y ，Zhang R ，Deng Y ，Li D ... -  《Frontiers in Immunology》

The pathogenic role of innate lymphoid cells in autoimmune-related and inflammatory skin diseases.

Zhou S ，Li Q ，Wu H ，Lu Q ... -  《-》

Role of fibroblasts in nonfibrotic autoimmune skin diseases.

Autoimmune diseases, a disease characterized by immune imbalance caused by the human immune system mistakenly attacking its own components, include vitiligo, psoriasis and atopic dermatitis (AD). Previous studies on autoimmune diseases have focused mainly on immune cells, keratinocytes and endothelial cells. Fibroblasts, the main cells that secrete the extracellular matrix (ECM) in the dermis, have been studied thoroughly in terms of fibrosis and wound healing. However, an increasing number of studies have shown that fibroblasts play an important role in nonfibrotic autoimmune skin diseases. In this article, the previously reported role of fibroblasts in nonfibrous autoimmune skin diseases such as psoriasis, vitiligo and AD is summarized to provide new ideas for the treatment of this disease.

He Y ，Han Z ，Zhang Q ，Liu L ，Chang J ... -  《-》

The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

Lin Y ，Wu X ，Yang Y ，Wu Y ，Xiang L ，Zhang C ... -  《Frontiers in Immunology》