Mutation of ROR γT reveals a role for Th17 cells in both injury and recovery from renal ischemia reperfusion injury.

Mutation of RORγT reveals a role for Th17 cells in both injury and recovery from renal ischemia reperfusion injury. Am J Physiol Renal Physiol. 2020 Sep 14;: Authors: Mehrotra P, Ullah MM, Collett JA, Myers SL, Dwinell MR, Geurts AM, Basile DP Abstract To investigate Th17 cells in the setting of acute kidney injury (AKI), the master regulator of Th17 cell differentiation, RORγT, was mutated in Lewis rats using CRISPR/Cas9 technology. In response to 40 min bilateral renal I/R, Rorc-/- rats were resistant to injury relative to wild-type Rorc+/+ rats. This protection was associated with inhibition of IL17 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 Rorc-/- rats. This maneuver equalized the initial level of injury in Rorc-/- and Rorc+/+ rats 1 to 2 days post I/R based on serum creatinine values. However Rorc-/- rats, but not Rorc+/+ rats, failed to successfully recover renal function and had high mortality by 4 days post I/R. Kidney tubules from Rorc+/+ rats showed evidence of repair by day-4 post I/R, while Rorc-/- rats showed persistent necrosis and elevated cell proliferation. Adoptive transfer of CD4+ cells from spleen of Rorc+/+ rats or supplementation of exogenous rIL17 by osmotic mini-pump improved renal function and survival of Rorc-/- rats following 50 min of I/R. This was associated with a relative d...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research