{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:06:01Z","timestamp":1773457561312,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Notch signaling is involved in regulating TLR-mediated responses in activated macrophages. In this study, we investigated the impact of Notch signaling in macrophages in an experimental autoimmune encephalomyelitis (EAE) model. To examine the impact of deficiency in Notch signaling in activated macrophages in EAE, an adoptive transfer of activated macrophages derived from Notch1fl\/fl \u00d7 Mx1cre+\/\u2212 (Notch1 knockout [N1KO]) or CSL\/Rbp-j\u03bafl\/fl \u00d7 Mx1cre+\/\u2212 (CSL\/RBP-J\u03ba KO) mice was performed prior to induction of EAE. Mice receiving activated N1KO macrophages showed decreased severity of EAE compared with mice receiving wild-type or CSL\/RBP-J\u03ba KO macrophages. In vitro restimulation of splenocytes by myelin oligodendrocyte glycoprotein 35\u201355 peptide from these mice revealed that cells from mice receiving N1KO macrophages produced significantly less IL-17 compared with the control mice, whereas IFN-\u03b3 production was similar in both groups. We found that activated N1KO, but not CSL\/RBP-J\u03ba KO, macrophages produced less IL-6 and had lower CD80 expression compared with wild-type and did not exhibit any defect in IL-12p40\/70 production, whereas activated macrophages from CSL\/RBP-J\u03ba KO mice phenocopied \u03b3-secretase inhibitor treatment for reduced IL-12p40\/70 production. Furthermore, the nuclear translocation of the NF-\u03baB subunit c-Rel was compromised in \u03b3-secretase inhibitor\u2013treated and CSL\/RBP-J\u03ba KO but not N1KO macrophages. These results suggest that Notch1 and CSL\/RBP-J\u03ba in macrophages may affect the severity of EAE differently, possibly through modulating IL-6 and CD80 expression, which is involved in the Th17 but not Th1 response.<\/jats:p>","DOI":"10.4049\/jimmunol.1401770","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T02:13:34Z","timestamp":1445912014000},"page":"5337-5346","source":"Crossref","is-referenced-by-count":24,"title":["Impact of Notch1 Deletion in Macrophages on Proinflammatory Cytokine Production and the Outcome of Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1093","volume":"195","author":[{"given":"Wipawee","family":"Wongchana","sequence":"first","affiliation":[{"name":"Graduate Program in Biotechnology, Faculty of Science, Chulalongkorn University , Bangkok 10330 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca G","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-0556","authenticated-orcid":false,"given":"Barbara A","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts , Amherst, MA 01003"},{"name":"Molecular and Cellular Biology Program, University of Massachusetts , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanapat","family":"Palaga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Omics Sciences and Bioinformatics Center, Chulalongkorn University , Bangkok 10330 ,","place":["Thailand"]},{"name":"Center of Excellence in Immunology and Immune-mediated Diseases, Chulalongkorn University , Bangkok 10330 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"2025030704250633500_r1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1146\/annurev.immunol.23.021704.115747","article-title":"Regulation of lymphoid development, differentiation, and function by the Notch pathway","volume":"23","author":"Maillard","year":"2005","journal-title":"Annu. 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