Transcriptional Regulators of T Helper 17 Cell Differentiation in Health and Autoimmune Diseases

Abstract

T helper (Th) 17 cells are a subtype of CD4 T lymphocytes characterized by the expression of retinoic acid-receptor (RAR)-related orphan receptor (ROR)γt transcription factor, encoded by gene Rorc. These cells are implicated in the pathology of autoimmune inflammatory disorders as well as in the clearance of extracellular infections. The main function of Th17 cells is the production of cytokine called interleukin (IL)-17A. This review highlights recent advances in mechanisms regulating transcription of IL-17A. In particular, we described the lineage defining transcription factor RORγt and other factors that regulate transcription of Il17a or Rorc by interacting with RORγt or by binding their specific DNA regions, which may positively or negatively influence their expression. Moreover, we reported the eventual involvement of those factors in Th17-related diseases, such as multiple sclerosis, rheumatoid arthritis, psoriasis, and Crohn's disease, characterized by an exaggerated Th17 response. Finally, we discussed the potential new therapeutic approaches for Th17-related diseases targeting these transcription factors. The wide knowledge of transcriptional regulators of Th17 cells is crucial for the better understanding of the pathogenic role of these cells and for development of therapeutic strategies aimed at fighting Th17-related diseases.

COVID‐19 and Treg/Th17 imbalance: Potential relationship to pregnancy outcomes

“…44 CXCLs then attract myeloid cells such as neutrophils to infected or injured tissues. 44 In contrast, Treg cells express anti-inflammatory cytokines (IL-4, IL-10, and TGF-β) and control excessive immune responses. 45,46 The Treg/Th17 balance plays an important role in the severity of lung injury 47 and in uncontrolled systemic inflammation characterizing acute lung injury (ALI)/ ARDS ( Figure 1C).…”

“…These two CD4 + T‐cell subsets have different actions 43 . Th17 cells are mainly characterized by their production of inflammatory cytokines such as IL‐17A, 42 which activates target cells and induces chemokine (C–X–C motif) ligands (CXCLs) 44 . CXCLs then attract myeloid cells such as neutrophils to infected or injured tissues 44 .…”

Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

“…Further analysis found that RORC and S100A12 were associated with psoriasis severity. The nuclear receptor retinoic acid receptor-related orphan receptor gamma (murine form "RORγ" or human form "RORC") was a key transcription factor for the production of IL-17 and involved in in ammatory response of psoriasis [20] . Compared with severe psoriasis, mild psoriasis was characterized by higher IL-17A expression in psoriatic lesion [21] , which is consistent with the alteration of RORC in our study.…”

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

“…Th17s are a subtype of CD4-positive T cells specialized for mounting immune responses against fungi and some extracellular bacteria. In addition to IL-17A, Th17s produce IL-17F, IL-21, IL-22, and IL-26 (79). Because IL-17 is a potent proinflammatory cytokine that amplifies ongoing inflammation, aberrant regulation of Th17s contributes to development of inflammatory and autoimmune disorders.…”