Tissue fibroblasts are versatile immune regulators: an evaluation of their impact on the aging process

Fibroblasts are abundant stromal cells which not only control the integrity of extracellular matrix (ECM) but also act as immune regulators. It is known that the structural cells within tissues can establish an organ-specific immunity expressing many immune-related genes and closely interact with immune cells. In fact, fibroblasts can modify their immune properties to display both pro-inflammatory and immunosuppressive activities in a context-dependent manner. After acute insults, fibroblasts promote tissue inflammation although they concurrently recruit immunosuppressive cells to enhance the resolution of inflammation. In chronic pathological states, tissue fibroblasts, especially senescent fibroblasts, can display many pro-inflammatory and immunosuppressive properties and stimulate the activities of different immunosuppressive cells. In return, immunosuppressive cells, such as M2 macrophages and myeloid-derived suppressor cells (MDSC), evoke an excessive conversion of fibroblasts into myofibroblasts, thus aggravating the severity of tissue fibrosis. Single-cell transcriptome studies on fibroblasts isolated from aged tissues have confirmed that tissue fibroblasts express many genes coding for cytokines, chemokines, and complement factors, whereas they lose some fibrogenic properties. The versatile immune properties of fibroblasts and their close cooperation with immune cells indicate that tissue fibroblasts have a crucial role in the aging process and age-related diseases.