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We previously confirmed that loss of ERAP1 functions resulted in exaggerated innate immune responses in a murine in vivo model. Here, we investigated the role of ERAP1 in suppressing inflammasome pathways and their dependence on ER stress responses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Using bone marrow-derived macrophages (BMDMs), we found that loss of ERAP1 in macrophages resulted in exaggerated production of IL-1\u03b2 and IL-18 and augmented caspase-1 activity, relative to wild type macrophages. Moreover, an in vivo colitis model utilizing dextran sodium sulfate (DSS) confirmed increased levels of proinflammatory cytokines and chemokines in the colon of DSS treated ERAP1<jats:sup>\u2212\/\u2212<\/jats:sup> mice as compared to identically stimulated WT mice. Interestingly, stimulated ERAP1<jats:sup>\u2212\/\u2212<\/jats:sup> BMDMs and CD4<jats:sup>+<\/jats:sup> T cells simultaneously demonstrated exaggerated ER stress, assessed by increased expression of ER stress-associated genes, a state that could be reverted to WT levels with use of the ER stress inhibitor Tauroursodeoxycholic acid (TUDCA).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Together, these results not only suggest that ERAP1 is important for regulating inflammasome dependent innate immune response pathways in vivo, but also propose a mechanism that underlies these changes, that may be associated with increased ER stress due to lack of normal ERAP1 functions.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12865-022-00481-9","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:38:34Z","timestamp":1646401114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["ERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses"],"prefix":"10.1186","volume":"23","author":[{"given":"Maja K.","family":"Blake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Pepelyayeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Godbehere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Aldhamen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Amalfitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"481_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.04.007","author":"A Fierabracci","year":"2012","unstructured":"Fierabracci A, Milillo A, Locatelli F, Fruci D. 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Care for mice was provided in accordance with PHS and AAALAC regulations. All methods here are reported in accordance with ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors have no financial competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9"}}