Fibroblasts as confederates of the immune system

Abstract

| 147 wileyonlinelibrary.com/journal/imr 1 | INTRODUC TI ON "Stromal" cell refers to the cellular component that form and maintain the structural parts of an organ, whereas parenchymal cells perform the specific organ function. Stromal cells, such as fibroblasts, have traditionally been considered as quiescent cells that primarily function to make extracellular matrices. Relevant in the clinic, these cells contribute to excessive connective tissue formation during injury repair, cancer, and fibrosis. However, these dedicated cells, and the niches they create, also orchestrate immunological functions by influencing the differentiation, movement, and activation of immune cells. Recent genetic lineage-tracing and single-cell RNA sequencing studies highlight the diversity of stromal cell populations in tissues and revealed how eclectic stromal cells orchestrate the diversity of immunological functions.These days, fibroblasts are no longer considered as mere structural components of organs but as dynamic participants in immune processes. We discuss four major mechanisms by which fibroblasts and immune cells interact: (a) paracrine signaling via cytokine and chemokine secretion, (b) direct priming via juxtacrine interactions, and (c) behavioral modulation through extracellular matrix remodeling. Finally, and more recently described, (d) transfer or mobilization of extracellular matrix microenvironments. In the following sections, we review the impact of these four modes of interaction between distinct fibroblast populations and immune cells during homeostasis, injury repair, scarring, and disease in the mammalian skin. Finally, we discuss the origins, of these and other stromal lineages, and their

Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19

“…S4C), and could reflect different maturation states of the ongoing fibrosis with a transition from microenvironments characterized by a more endothelial-dominated towards a mesenchymal signature, a process known as endothelial to mesenchymal transition (EndMT) 20 . Accordingly, C5 showed features of constitutive connective tissue associated with intermediate-to-large vessels 1 , while C9 also included endothelial-related genes, suggestive of recently generated, capillary-rich fibrous tissue 21 , and showed a strong expression of CCL21 (Fig. S4A-C and Fig.…”

Eosinophil-Derived Osteopontin Induces the Expression of Pro-Inflammatory Mediators and Stimulates Extracellular Matrix Production in Nasal Fibroblasts: The Role of Osteopontin in Eosinophilic Chronic Rhinosinusitis

“…The fibroblasts are the main cells to synthesize collagen and contribute to tissue regeneration ( 19 , 20 ). Moreover, fibroblasts not only play a role in tissue organization, but also contribute to the immune response via cytokine secretion ( 18 , 29 ). As for the relationship between eosinophils with fibroblasts, eosinophils stimulate fibroblasts to increase the production of extracellular matrix and induce tissue fibrogenesis ( 30 ).…”

Furnishing Wound Repair by the Subcutaneous Fascia

“…Physiological functions of subcutaneous fascia is ensured by additional tasks taken up by its resident fibroblasts including: (1) balancing extracellular matrix production and its modification by modulating matrix metalloproteinases (MMPs) and their inhibitors-tissue inhibitors of metalloproteinases (TIMPs) [3]; (2) maintaining stromal cell homeostasis by releasing growth factors such as connective tissue growth factor (CTGF/CCN2), transforming growth factor-beta (TGF-β), and fibroblast growth factor (FGF) [8]; (3) controlling inflammatory responses by interacting with and providing a niche for recruited immune cells [28]; and (4) maintaining balanced interstitial fluid pressure by regulating fluid pressure and flow that permeate through the fascia. When the fascial fibroblast undergoes a strain, the water inside is expelled toward the extracellular matrix.…”