To investigate T helper type 17 (Th17) cells in the setting of acute kidney injury, the gene encoding the master regulator of Th17 cell differentiation, that is, RAR-related orphan receptor-γ (RORγT), was mutated in Lewis rats using CRISPR/Cas9 technology. In response to 40 min of bilateral renal ischemia-reperfusion (I/R), RAR-related orphan receptor C () rats were resistant to injury relative to wild-type rats. This protection was associated with inhibition of IL-17 expression and reduced infiltration of CD4 cells, CD8 cells, B cells, and macrophages. To evaluate the effect of Th17 cells on repair, ischemia was increased to 50 min in rats. This maneuver equalized the initial level of injury in and rats 1 to 2 days post-I/R based on serum creatinine values. However, rats, but not rats, failed to successfully recover renal function and had high mortality by 4 days post-I/R. Histological assessment of kidney tubules showed evidence of repair by post-I/R in rats but persistent necrosis and elevated cell proliferation in rats. Adoptive transfer of CD4 cells from the spleen of rats or supplementation of exogenous rIL-17 by an osmotic minipump improved renal function and survival of rats following 50 min of I/R. This was associated with a relative decrease in the number of M-type macrophages and a relative increase in the percentage of T regulatory cells. Taken together, these data suggest that Th17 cells have both a deleterious and a beneficial role in kidney injury and recovery, contributing to early postischemic injury and inflammation but also possibly being critical in the resolution of inflammation during kidney repair.

American journal of physiology. Renal physiology

5

2020

https://journals.physiology.org/doi/10.1152/ajprenal.00187.2020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

Am J Physiol Renal Physiol