Fibroblast heterogeneity and its role in generating protective immunity in the secondary lymphoid organs

Hadida Yasmin ¹ Ann Mary Joseph ² Uday Kishore ^2*

• ¹ Cooch Behar Panchanan Barma University, Koch Bihār, West Bengal, India
• ² Biosciences, United Arab Emirates University, Al-Ain, United Arab Emirates

Fibroblasts are cells of mesenchymal origin with a range of phenotypic diversity and heterogeneity. One of the major functions of fibroblasts is the formation and turnover of extracellular matrix (ECM) and establishing a tissue structure by forming a matrisome from embryonic development to adult stage. It plays an indispensable role in ECM remodeling during injury, repair and infection providing a scaffold for cell-to-cell interaction. Despite their important pathophysiological roles, molecular markers for tissue-resident fibroblasts are now being identified. Based on their residency, fibroblasts acquire molecular signatures based on anatomical locations, thus, impacting on their phenotypic heterogeneity despite their overlapping morphology. Fibroblasts are now recognized as key immune sentinel cells, capable of regulating the inflammatory milieu through its distinct functional subsets that are designed to respond differently with unique immune signatures. Fibroblasts can detect the pathogenic and danger signals through its diverse pattern recognition receptors (PRRs) and release soluble mediators that can modulate the immune infiltrates to the site of tissue injury and repair. This review discusses the diversity and heterogeneity of fibroblasts in secondary lymphoid organs such as lymph node, spleen and Peyer’s patches and their contributions to a range of pathological and physiological processes. The role of trans-differentiated effector fibroblast phenotypes that modulate the expression and function of various innate immune components (PRRs, cytokines, chemokines, and complement) in maintaining the homeostasis has also been discussed.