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However, the in vivo relevance of this regulatory circuit is unknown. We generate IRF2\n                    <jats:sup>KO<\/jats:sup>\n                    mice and demonstrate that they are equally susceptible to\n                    <jats:italic>Francisella novicida<\/jats:italic>\n                    infection as GSDMD\n                    <jats:sup>KO<\/jats:sup>\n                    mice. Interestingly, the phenotypes of IRF2\n                    <jats:sup>KO<\/jats:sup>\n                    and GSDMD\n                    <jats:sup>KO<\/jats:sup>\n                    mice diverge with respect to IFN-\u03b3. Specifically, IRF2\n                    <jats:sup>KO<\/jats:sup>\n                    mice exhibit a profound defect in IFN-\u03b3 production, which we attribute to an intrinsic role of IRF2 in regulating both the number and maturation of NK cells. IRF2\n                    <jats:sup>KO<\/jats:sup>\n                    NK cells fail to express the antibacterial effectors IL-18R and Granzyme A, thereby impairing bacterial clearance. IFN-\u03b3 therapy partially restores immune responses in IRF2\n                    <jats:sup>KO<\/jats:sup>\n                    mice and resistance to infection. These findings confirm IRF2 as a dual regulator of inflammasome activity and NK cell function, highlighting its pivotal role in innate immunity. Moreover, they underscore the potential of IFN-\u03b3 therapy as a promising treatment for severe infections in patients with primary immunodeficiencies affecting multiple immune pathways.\n                  <\/jats:p>","DOI":"10.1038\/s44319-026-00698-4","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:22:04Z","timestamp":1769617324000},"page":"1325-1352","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRF2 deficiency disrupts pyroptosis, NK cell interferon-\u03b3 production and resistance to Francisella"],"prefix":"10.1038","volume":"27","author":[{"given":"Maxence","family":"Cornut","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-5387","authenticated-orcid":false,"given":"Sophia","family":"Djebali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Rondeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Dayet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Th\u00e9o","family":"Fayolle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Haagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Fallone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00e9mi","family":"Rousseaux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Caspar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9lissa","family":"Marcotte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amandine","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Courteboeuf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u00eblan","family":"Deschamps-Biboulet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Marvel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9n\u00e9dicte F","family":"Py","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-8179","authenticated-orcid":false,"given":"Thierry","family":"Walzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Marcais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-8565","authenticated-orcid":false,"given":"Thomas","family":"Henry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-5478","authenticated-orcid":false,"given":"\u00c9milie","family":"Bourdonnay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"698_CR1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0882-4010(89)90022-3","volume":"7","author":"LS Anthony","year":"1989","unstructured":"Anthony LS, Ghadirian E, Nestel FP, Kongshavn PA (1989) The requirement for gamma interferon in resistance of mice to experimental tularemia. 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