Publication: Canonical IRE1 function needed to sustain vigorous natural killer cell proliferation during viral infection

Publié dans: iScience, 2023, 26 (12), pp.108570. ⟨10.1016/j.isci.2023.108570⟩

Auteurs: Jessica Vetters, Mary van Helden, Clint de Nolf, Sofie Rennen, Eva Cloots, Evelien van de Velde, Farzaneh Fayazpour, Justine van Moorleghem, Manon Vanheerswynghels, Karl Vergote, Louis Boon, Eric Vivier, Bart N Lambrecht, Sophie Janssens

Résumé

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.

Lien vers HAL – amu-04542884

Lien vers le DOI – 10.1016/j.isci.2023.108570