{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:39:40Z","timestamp":1776040780677,"version":"3.50.1"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ubiquitination was recently identified as a central process in the pathogenesis and development of numerous inflammatory diseases, such as obesity, atherosclerosis, and asthma. Treatment with proteasomal inhibitors led to severe side effects because ubiquitination is heavily involved in a plethora of cellular functions. Thus, new players regulating ubiquitination processes must be identified to improve therapies for inflammatory diseases. In addition to their role in adaptive immunity, endosomal MHC class II (MHCII) molecules were shown to modulate innate immune responses by fine tuning the TLR4 signaling pathway. However, the role of MHCII ubiquitination by membrane associated ring-CH-type finger 1 (MARCH1) E3 ubiquitin ligase in this process remains to be assessed. In this article, we demonstrate that MARCH1 is a key inhibitor of innate inflammation in response to bacterial endotoxins. The higher mortality of March1\u2212\/\u2212 mice challenged with a lethal dose of LPS was associated with significantly stronger systemic production of proinflammatory cytokines and splenic NK cell activation; however, we did not find evidence that MARCH1 modulates LPS or IL-10 signaling pathways. Instead, the mechanism by which MARCH1 protects against endotoxic shock rests on its capacity to promote the transition of monocytes from Ly6CHi to Ly6C+\/\u2212. Moreover, in competitive bone marrow chimeras, March1\u2212\/\u2212 monocytes and polymorphonuclear neutrophils outcompeted wild-type cells with regard to bone marrow egress and homing to peripheral organs. We conclude that MARCH1 exerts MHCII-independent effects that regulate the innate arm of immunity. Thus, MARCH1 might represent a potential new target for emerging therapies based on ubiquitination reactions in inflammatory diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1601168","type":"journal-article","created":{"date-parts":[[2016,12,10]],"date-time":"2016-12-10T03:21:21Z","timestamp":1481340081000},"page":"852-861","source":"Crossref","is-referenced-by-count":35,"title":["MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice"],"prefix":"10.1093","volume":"198","author":[{"given":"Tristan","family":"Galbas","sequence":"first","affiliation":[{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montreal , Montreal, Quebec H3T 1J4,","place":["Canada"]},{"name":"Laboratoire d\u2019Immunologie Mol\u00e9culaire, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec H3T 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Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montreal , Montreal, Quebec H3T 1J4,","place":["Canada"]},{"name":"Immunology-Oncology Section, Research Center, Maisonneuve-Rosemont Hospital , Montreal, Quebec H1T 2M4,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheolho","family":"Cheong","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montreal , Montreal, Quebec H3T 1J4,","place":["Canada"]},{"name":"Laboratoire de Physiologie Cellulaire et Immunologie, Institut de Recherches Cliniques de Montr\u00e9al , Montreal, Quebec H2W 1R7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Thibodeau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montreal , Montreal, Quebec H3T 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