Th17 and regulatory T lymphocytes in primary biliary cirrhosis and systemic sclerosis as models of autoimmune fibrotic diseases.

Fibrotic autoimmune diseases are characterized by an inflammatory process in which fibrogenic cytokines, such as TGFβ and IL6, have a major role. Interestingly, these cytokines are also involved in the generation and function of both an effector T lymphocyte subpopulation, the Th17 cells, and the regulatory T lymphocytes (Treg). These evidences raised the hypothesis that an unbalanced equilibrium induced by the overproduction of the fibrogenic cytokines may have pathogenic relevance in fibrotic autoimmune diseases. On this basis, this review analyzes the available data concerning Th17 and Treg generation and function in two representative fibrotic autoimmune diseases, primary biliary cirrhosis (PBC) and systemic sclerosis (SSc), as models for organ-specific and systemic diseases, respectively. With regard to the Th17 cells, their expansion was found to be a common feature associated with a relative contraction of Th1 immune responses. Concerning to the regulatory T cell compartment, quantitative and qualitative alterations were observed in both diseases. However, while PBC patients showed defects only in the CD8+ Treg subset, SSc patients demonstrated abnormalities regarding to both the CD4+CD25+ and the CD8+ Treg subpopulations. Hence, the CD8+ Treg subset seems to be the most involved in the pathogenic cascade leading to fibrotic disease onset and maintenance. Collectively, the reviewed data support the concept that altered homeostasis between effector and regulatory T cell circuits is present in fibrotic autoimmune diseases and that the major factors responsible for such disequilibrium are Th17 cells in the effector arm and CD8+ Treg in the regulatory arm.