EVIDENCE OF FIBROBLAST HETEROGENEITY AND THE ROLE OF FIBROBLAST SUBPOPULATIONS IN FIBROSIS

This review article highlights the evidence supporting the concept tha t, like lymphocytes, fibroblasts also consist of subpopulations with u nique phenotypes and functions. A new view of the fibroblast is that t hey are dynamic and consist of subsets which produce cytokines and int eract with the immune system. For example, murine lung fibroblasts sep arated by fluorescence-activated cell sorting on the basis of the thym ocyte-1 antigen are heterogeneous in their morphology, expression of s urface markers, antigen presentation to T lymphocytes, ability to synt hesize collagen, and cytokine production. Human lung fibroblasts have also been found to be heterogeneous in surface marker expression, prol iferation, and collagen production. Investigation of pulmonary fibrobl ast heterogeneity is important since the lung is particularly suscepti ble to fibrosis induced by chemotherapy and radiation, inhaled particl es, systemic autoimmune disease, etc. The inflammatory responses which typically precede fibrotic induction may be controlled by a subset of resident fibroblasts. Another subset may be important for the fibrobl ast hyperplasia and extensive extracellular matrix production which ar e hallmarks of fibrosis. In another model system, periodontal fibrobla sts, namely those from periodontal ligament (PDL) and gingiva, also re veal heterogeneity. For example, PDL fibroblasts are composed of subpo pulations based on collagen production, morphology, and glycogen pools . Subsets of gingival fibroblasts have also been obtained based on rec eptors for cyclosporin A and Clq. Specific fibroblast subsets may be i nvolved in gingival repair and hyperplasia. Studies comparing fibrobla sts from normal skin vs skin involved with scleroderma have found that scleroderma fibroblasts are activated and able to participate in an i nflammatory response. How these fibroblasts become activated is unclea r, but it is believed that a subset of fibroblasts is selectively recr uited by cytokines at the inflammation site. Finally, investigation an d identification of fibroblast subsets from various tissues and their interaction with the immune system could lead to strategies to prevent or reverse debilitating and potentially fatal fibrotic development. ( C) 1994 Academic Press, Inc.