Figure 4.

Functional heterogeneity of resident fibroblasts in the kidney. Resident fibroblasts in the kidney are a plastic population that can adopt a wide range of phenotypes dependent on their surrounding microenvironment.^{6,11,32,50,51,59)} (A) In response to injury, fibroblasts transdifferentiate into myofibroblasts, some of which acquire the ability to produce retinoic acid (RA). Although RA derived from myofibroblasts can support the regeneration of tubular cells,³²⁾ RA in aged injured kidneys additionally promotes the transdifferentiation of fibroblasts into tertiary lymphoid tissue (TLT)-associated fibroblasts,^6,50,51) suggesting that RA signaling in the injured kidney appears to be context dependent. Resident fibroblasts within the TLT produce CXCL13 and CCL19, playing a central role in TLT formation and maintenance. In IgG4-related disease, fibroblasts express strong expression of glucocorticoid receptor. (B) Multiple roles of resident fibroblasts in healthy and diseased kidney. αSMA: α-smooth muscle actin, ECM: extracellular matrix, EPO: erythropoietin, GR: glucocorticoid receptor, IgG4-RD: IgG4-related disease, p75NTR: p75 neurotrophin receptor, RALDH: retinaldehyde dehydrogenase.