Tissue-Resident NK Cells Mediate XXXX and Are Not Depleted by Anti-Asialo-GM1 Antibody.

@entity8 @entity63 @entity19 @entity14737 @entity11386 @entity281 @entity19985
UNASSIGNED: NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, @entity281 . Whereas conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. In the present study, we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying @entity63 in the @entity19 kidney. Parabiosis experiments demonstrate that the kidney contains a significant fraction of trNK cells under homeostatic conditions. Kidney trNK cells developed independent of @entity14737 and @entity19985 , and they expressed a distinct cell surface phenotype as compared with cNK cells. Among these, trNK cells had reduced asialo-GM1 (AsGM1) expression relative to cNK cells, a phenotype observed in trNK cells across multiple organs and @entity19 strains. Strikingly, anti-AsGM1 Ab treatment, commonly used as an NK cell-depleting regimen, resulted in a robust and selective depletion of cNKs, leaving trNKs largely intact. Using this differential depletion, we tested the relative contribution of cNK and trNK cells in @entity8 . Whereas anti- @entity11386 Ab effectively depleted both trNK and cNK cells and protected against @entity63 /reperfusion injury, anti-AsGM1 Ab preferentially depleted cNK cells and failed to protect against injury. These data demonstrate unanticipated specificity of anti-AsGM1 Ab depletion on NK cell subsets and reveal a new approach to study the contributions of cNK and trNK cells in vivo. In total, these data demonstrate that trNK cells play a key role in modulating local responses to @entity63 tissue injury in the kidney and potentially other organs.
