{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:56:47Z","timestamp":1792724207105,"version":"4.5.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,31]]},"abstract":"<jats:p>\n                    Increasing evidence highlights a role for the immune system in the pathogenesis of autism spectrum disorder (ASD), as immune dysregulation is observed in the brain, periphery, and gastrointestinal tract of ASD individuals. Furthermore, maternal infection (maternal immune activation, MIA) is a risk factor for ASD. Modeling this risk factor in mice yields offspring with the cardinal behavioral and neuropathological symptoms of human ASD. In this study, we find that offspring of immune-activated mothers display altered immune profiles and function, characterized by a systemic deficit in CD4\n                    <jats:sup>+<\/jats:sup>\n                    TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    T regulatory cells, increased IL-6 and IL-17 production by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and elevated levels of peripheral Gr-1\n                    <jats:sup>+<\/jats:sup>\n                    cells. In addition, hematopoietic stem cells from MIA offspring exhibit altered myeloid lineage potential and differentiation. Interestingly, repopulating irradiated control mice with bone marrow derived from MIA offspring does not confer MIA-related immunological deficits, implicating the peripheral environmental context in long-term programming of immune dysfunction. Furthermore, behaviorally abnormal MIA offspring that have been irradiated and transplanted with immunologically normal bone marrow from either MIA or control offspring no longer exhibit deficits in stereotyped\/repetitive and anxiety-like behaviors, suggesting that immune abnormalities in MIA offspring can contribute to ASD-related behaviors. These studies support a link between cellular immune dysregulation and ASD-related behavioral deficits in a mouse model of an autism risk factor.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1202556109","type":"journal-article","created":{"date-parts":[[2012,7,17]],"date-time":"2012-07-17T09:21:03Z","timestamp":1342516863000},"page":"12776-12781","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":317,"title":["Modeling an autism risk factor in mice leads to permanent immune dysregulation"],"prefix":"10.1073","volume":"109","author":[{"given":"Elaine Y.","family":"Hsiao","sequence":"first","affiliation":[{"name":"Biology Division, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara W.","family":"McBride","sequence":"additional","affiliation":[{"name":"Biology Division, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Chow","sequence":"additional","affiliation":[{"name":"Biology Division, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarkis K.","family":"Mazmanian","sequence":"additional","affiliation":[{"name":"Biology Division, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Biology Division, California Institute of Technology, Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,7,16]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1","article-title":"Prevalence of autism spectrum disorders\u2014Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008","volume":"61","author":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators","year":"2012","unstructured":"; Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, Prevalence of autism spectrum disorders\u2014Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. 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