| First Author | Vetters J | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 12 | Pages | 108570 |
| PubMed ID | 38162021 | Mgi Jnum | J:351157 |
| Mgi Id | MGI:7572041 | Doi | 10.1016/j.isci.2023.108570 |
| Citation | Vetters J, et al. (2023) Canonical IRE1 function needed to sustain vigorous natural killer cell proliferation during viral infection. iScience 26(12):108570 |
| abstractText | The unfolded protein response (UPR) aims to restore ER homeostasis under conditions of high protein folding load, a function primarily serving secretory cells. Additional, non-canonical UPR functions have recently been unraveled in immune cells. We addressed the function of the inositol-requiring enzyme 1 (IRE1) signaling branch of the UPR in NK cells in homeostasis and microbial challenge. Cell-intrinsic compound deficiency of IRE1 and its downstream transcription factor XBP1 in NKp46(+) NK cells, did not affect basal NK cell homeostasis, or overall outcome of viral MCMV infection. However, mixed bone marrow chimeras revealed a competitive advantage in the proliferation of IRE1-sufficient Ly49H(+) NK cells after viral infection. CITE-Seq analysis confirmed strong induction of IRE1 early upon infection, concomitant with the activation of a canonical UPR signature. Therefore, we conclude that IRE1/XBP1 activation is required during vigorous NK cell proliferation early upon viral infection, as part of a canonical UPR response. |
