Helminth exposure influences Th17 plasticity, suppressing inflammatory and promoting regulatory activity by Th17...

Many autoimmune and inflammatory-mediated diseases are driven by pathogenic Th17 responses. Infection with parasitic worms (helminths) alters host immune responses, suppresses Th17 activity and can inhibit pathogenic inflammation. Instead of being terminally differentiated, Th17 cells are plastic and can assume highly pathogenic Th1-like function or more regulatory Tr1/Treg-like function. We investigated if helminth infection influences this Th17 plasticity.

Lymphocytes from Th17-reporter mice permanently express eYFP if they previously transcribed IL-17. Using these mice, we examined if exposure to the intestinal helminth Heligmosomoides polygyrus bakeri altered the in vitro and in vivo regulatory activity of Th17 lineage cells.

We found that exposure intestinal helminths alter the Th17 compartment inhibiting development of Th1-like Th17 cells and promoting development of Tr1/Treg-like cells from the Th17 lineage. Furthermore, Th17 lineage cells from helminth-infected mice suppressed T cell proliferation and inhibited T cell-transfer colitis.

Thus, intestinal helminth-exposure not only reduces the frequency of Th17 cells in the MLN cell population, but in addition, changes the behavior of the remaining Th17-lineage cells to function more like classical T regulatory cells.