Dermal fibroblast subsets and their roles in inflammatory and autoimmune skin diseases

Fibroblasts are mesenchymal cells that constitute the stroma across tissues. Historically, they have long been perceived as uniform structural cells passively residing in the background during the immune responses within tissues. However, a growing number of recent studies have revealed that fibroblasts are highly heterogeneous and dynamic, responding to various external stimuli with notable plasticity. They exhibit heterogeneity not only across tissues but also within the same organ, and show dynamic changes over time throughout development and aging. As a barrier tissue, the skin is constantly exposed to numerous environmental stressors and pathogens and is capable of mounting diverse yet robust immune responses to these stimuli. Reflecting this inherent nature, skin dermal fibroblasts are remarkably heterogeneous and dynamic. Upon tissue inflammation, they produce and secrete not only inflammatory cytokines and chemokines but also extracellular matrix molecules that critically modulate immune cell infiltration. They also engage in direct mechano-chemical interactions with neighboring cells and actively support neural growth. Furthermore, they function as antigen presenting cells and contribute to the formation of tertiary lymphoid structures. This review highlights recent advances in understanding the heterogeneity of dermal fibroblast subpopulations and their roles in the pathogenesis of major inflammatory and autoimmune skin diseases.