{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:05:52Z","timestamp":1779303952813,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Genetics","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Animals must differentially allocate essential metabolic resources in response to changing environmental conditions to ensure reproductive success. For example, adult\n                  <jats:italic>C. elegans<\/jats:italic>\n                  coordinate innate immune defenses during infection and also allocate fat stores to the germline, each of which are required for evolutionary fitness. The genetic mechanisms that integrate resource allocation and host defenses in this context, however, are not fully understood. From a forward genetic screen for novel regulators of innate immune gene transcription, we identified\n                  <jats:italic>kri-1<\/jats:italic>\n                  , the nematode homolog of human Krev interaction trapped protein\n                  <jats:italic>KRIT1<\/jats:italic>\n                  . Mutations in human\n                  <jats:italic>KRIT1<\/jats:italic>\n                  underlie cerebral cavernous malformations, a disease marked by defects in vascular integrity. Similarly,\n                  <jats:italic>C. elegans kri-1\/KRIT1<\/jats:italic>\n                  is required for the integrity of the intestinal epithelial cell barrier. We find also that\n                  <jats:italic>kri-1\/KRIT1<\/jats:italic>\n                  is required for host tolerance to bacterial infection, fecundity, and normal development. In this context,\n                  <jats:italic>kri-1\/KRIT1<\/jats:italic>\n                  restrains the activity of the cytoprotective transcription factor\n                  <jats:italic>skn-1\/NRF2<\/jats:italic>\n                  to control immune gene transcription and intestinal lipid mobilization during aging, a process necessary for healthy reproduction, but functions independently of\n                  <jats:italic>skn-1<\/jats:italic>\n                  \/\n                  <jats:italic>NRF2<\/jats:italic>\n                  to promote epithelial integrity and pathogen tolerance. These data reveal a broad role for a strongly conserved regulator in essential physiological processes that are required for reproductive fidelity and evolutionary success.\n                <\/jats:p>","DOI":"10.64898\/2026.05.15.725342","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:35:17Z","timestamp":1779154517000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>kri-1\/KRIT1<\/i>\n                  restrains\n                  <i>skn-1\/NRF2<\/i>\n                  activation to promote innate immune and lipid homeostasis"],"prefix":"10.64898","author":[{"given":"Akshay","family":"Alaghatta","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha Y.","family":"Tse-Kang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8961-2195","authenticated-orcid":false,"given":"Daniel","family":"Bollen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khursheed A.","family":"Wani","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas D.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5340-8294","authenticated-orcid":false,"given":"Read","family":"Pukkila-Worley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States of America;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026052011051551000_2026.05.15.725342v1.1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41577-025-01167-0","article-title":"Patterns of pathogenesis in innate immunity: 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