T Cells in Fibrosis and Fibrotic Diseases

Abstract

Fibrosis is the extensive deposition of fibrous connective tissue, and it is characterized by the accumulation of collagen and other extracellular matrix (ECM) components. Fibrosis is essential for wound healing and tissue repair in response to a variety of triggers, which include infection, inflammation, autoimmune disorder, degenerative disease, tumor, and injury. Fibrotic remodeling in various diseases, such as liver cirrhosis, pulmonary fibrosis, renal interstitial fibrosis, myocardial infarction, systemic sclerosis (SSc), and graft-versus-host disease (GVHD), can impair organ function, causing high morbidity and mortality. Both innate and adaptive immunity are involved in fibrogenesis. Although the roles of macrophages in fibrogenesis have been studied for many years, the underlying mechanisms concerning the manner in which T cells regulate fibrosis are not completely understood. The T cell receptor (TCR) engages the antigen and shapes the repertoire of antigen-specific T cells. Based on the divergent expression of surface molecules and cell functions, T cells are subdivided into natural killer T (NKT) cells, γδ T cells, CD8 + cytotoxic T lymphocytes (CTL), regulatory T (Treg) cells, T follicular regulatory (Tfr) cells, and T helper cells, including Th1, Th2, Th9, Th17, Th22, and T follicular helper (Tfh) cells. In this review, we summarize the pro-fibrotic or anti-fibrotic roles and distinct mechanisms of different T cell subsets. On reviewing the literature, we conclude that the T cell regulations are commonly disease-specific and tissue-specific. Finally, we provide perspectives on microbiota, viral infection, and metabolism, and discuss the current advancements of technologies for identifying novel targets and developing immunotherapies for intervention in fibrosis and fibrotic diseases.

Implications of microscale lung damage for COVID-19 pulmonary ventilation dynamics: A narrative review

“…These two functionally distinct CD4+ T cell populations thus may play a critical role in controlling alveolar fibrosis [ 91 ]. Readers interested in more detailed discussion of the role of T-cells in fibrosis are referred to a recent review by Zhang and Zhang [ 92 ].…”

Evaluation of hepatic fibrosis in HIV/HCV co-infected individuals in Yaoundé, Cameroon: usefulness of APRI score in resource-constrained settings

“…These results are similar to previous studies that found F2, F3 and F4 stages in 59.8% of HIV/HCV co-infected individuals and 46.6% of mono-infected, respectively [ 19 , 20 ]. This high rate of fibrosis is apparently link to the existence of a more active HCV infection supported by HIV-induced CD4 + T cell loss that deregulates T cell function leading to reduced anti-fibrotic activity of NK cells, resulting in accelerated progression of liver fibrosis in HIV/HCV co-infected participants [ 21 , 22 ].…”

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

“…While the pathophysiological role of the innate immune system in fibrogenesis and cirrhosis is well described, especially for HSC and hepatic macrophages, less studies are available on the exact role of the adaptive immune system. However, there is an emerging body of evidence describing important contributions of adaptive immune cells to chronic liver diseases and fibrosis [ 62 , 63 ]. Several studies point towards a profibrotic role of the T cell response whilst the progression of cirrhosis in turn disrupts T cell function [ 49 , 64 ].…”