Insight Into Non-Pathogenic Th17 Cells in Autoimmune Diseases

Abstract

Th17 cells are generally considered to be positive regulators of immune responses because they produce pro-inflammatory cytokines, including IL-17A, IL-17F, and IL-22. Cytokine production not only promotes accumulation of immune cells, such as macrophages, neutrophils and lymphocytes, at inflammatory sites but can also cause tissue pathologies. Conversely, certain Th17 cells can also negatively regulate immune responses by secreting immunosuppressive factors, such as IL-10; these cells are termed non-pathogenic Th17 cells. In this review, we summarize recent advances in the development and regulatory functions of non-pathogenic Th17 cells in autoimmune diseases.

Keywords: IL-10; Th17 cells; autoimmune diseases; immunosuppression; inflammation.

Figure 1

The role of non-pathogenic Th17 and pathogenic Th17 cells on autoimmune diseases. Naïve CD4⁺T cells stimulated with TGF-β3/IL-6, IL-1β/IL-6/IL-23, or TGF-β1/IL-6/IL-23 in vitro can secret inflammatory cytokines such as IL-17, IL-21, IL-22, and GM-CSF and express the specific transcription factor RORγt. Such Th17 cells that play important roles in the occurrence of autoimmune diseases are named by pathogenic Th17 cells. However, TGF-β1/IL-6-induced Th17 cells not only express RORγt but also express several IL-10-related transcription factors such as c-MAF, Ikzf3, and AhR. This type of Th17 cell expresses a low level of or lacks IL-23R but expresses a high level of CD5L/AIM and CD39 ectonucleotidases at the membrane. Adoptive transfer of Th17 cells induced by TGF-β1/IL-6 into wild-type mice does not cause EAE or T1D. In addition, a small fraction of Th17 cells in the intestine with suppressive function can also reduce IBD via IL-10 and TGF-β. However, the effect of non-pathogenic Th17 cells on RA requires further research in mice. EAE, experimental autoimmune encephalomyelitis; T1D, type 1 diabetes; RA, rheumatoid arthritis; IBD, inflammatory bowel disease.