Helper T cells are essential part of body's immune system. These cells are divided in many subsets based upon their ability to produce different cytokines. Following the discovery of interleukin-17 (IL-17) producing T helper (Th17) cells as a distinct lineage of T helper cells it became clear that these cells play an important role in the host defense and participate in the pathogenesis of many inflammatory and autoimmune diseases. The Th17 cells can alter their differentiation program ultimately giving rise to either protective or pro-inflammatory pathogenic cells. The protective and non-pathogenic Th17 cells are termed as Treg17 cells.
Contents
Activation
Like conventional regulatory T cells (Treg), induction of regulatory Treg17 cells could play an important role in modulating and preventing certain autoimmune diseases. Treg17 (Regulatory Th17) cells are generated from CD4+ T cells. Treg17 cells with regulatory phenotype with in vivo immune-suppressive properties in the gut have also been identified as rTh17 cells. Similar to Th17 cells the Treg17 development depended on the transcription factor Stat3.
Function
These regulatory Th17 cells are generated by TGF-beta plus IL-6 in vitro. They produce IL-17 and IL-10 and low level of IL-22 and suppress autoimmune and other immune responses. CD4+ T cells polarized with IL-23 and IL-6 are pathogenic upon adoptive transfer in type 1 diabetes while cells polarized with TGF-beta and IL-6 are not pathogenic., The intracellular aryl hydrocarbon receptor (AhR), which is activated by certain aromatic compounds, is specifically expressed in Treg17 cells. These cells are regulated by IL-23 and TGF-beta. The production of IL-22 in this subset of Th17 cells is regulated by AhR and Treg17 cells are depend on activation of the transcription factor Stat3. In a steady state, TGF-beta and AhR ligands induce low expression of IL-22 along with high expression of AhR, c-MAF, IL-10, and IL-21 that might play a protective role in cell regeneration and host microbiome homeostasis.
Clinical significance
Treg17 cells regulate the function of Th17 cells that are important role in the host defense against fungal and bacterial pathogens and participate in the pathogenesis of multiple inflammatory and autoimmune disorders. Selective deletion of Stat3 caused spontaneous severe colitis because of the lack of Treg17 cells and increase in pathogenic Th17 cells. The mechanism of Treg17 cell action is expression of chemokine receptor CCR6, which facilitates trafficking into areas of Th17 inflammation. This is also seen in human disease such Glomerulonephritis (GN) in kidney. Conversion of pathogenic Th17 cells in vivo at the conclusion of an inflammatory disease process by TGF-β results in the generation of Treg17 like cells. There is also conservation across species of Treg17 cells.