{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T15:46:57Z","timestamp":1770738417667,"version":"3.49.0"},"reference-count":47,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,3,2]]},"abstract":"<jats:p>Experimental autoimmune encephalomyelitis (EAE) is a T cell\u2013mediated autoimmune demyelinating disease of the central nervous system that serves as an animal model for multiple sclerosis. Antigen-specific tolerance regimens, including oral tolerance, have been used prophylactically to prevent development of acute EAE as well as a number of other autoimmune diseases. Two mechanisms have been proposed to explain the immunologic basis for disease inhibition: bystander immune suppression and clonal anergy\/deletion. This report demonstrates a novel mechanism for monocyte chemotactic protein (MCP)-1 as a regulatory factor of oral tolerance. Oral administration of proteolipid protein peptide (PLP139\u2013151) increased MCP-1 expression in the intestinal mucosa, Peyer's patch, and mesenteric lymph nodes. Increase in MCP-1 expression resulted in downregulation of mucosal interleukin (IL)-12 expression with concomitant increase in mucosal IL-4 expression. Functionally, MCP-1 upregulation was shown to regulate oral tolerance induction by the ability of antibodies to MCP-1 to inhibit tolerance induction. The anti\u2013MCP-1 abrogation of oral tolerance induction also resulted in restoration of mucosal IL-12 expression as well as peripheral antigen-specific T helper cell 1 responses. These results demonstrate a novel and important role for MCP-1 in the regulation or oral tolerance for the prevention and treatment of autoimmune disease.<\/jats:p>","DOI":"10.1084\/jem.187.5.733","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"733-741","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Monocyte Chemotactic Protein 1 Regulates Oral Tolerance Induction by Inhibition of T Helper Cell 1\u2013related Cytokines"],"prefix":"10.1084","volume":"187","author":[{"given":"William J.","family":"Karpus","sequence":"first","affiliation":[{"name":"From the *Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and \u2021Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"From the *Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and \u2021Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Kunkel","sequence":"additional","affiliation":[{"name":"From the *Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and \u2021Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas W.","family":"Lukacs","sequence":"additional","affiliation":[{"name":"From the *Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611; and \u2021Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1998,3,2]]},"reference":[{"key":"2023072508035855000_B1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.iy.10.040192.001101","article-title":"Immunologic aspects of demyelinating diseases","volume":"10","author":"Martin","year":"1992","journal-title":"Annu Rev Immunol"},{"key":"2023072508035855000_B2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0165-5728(92)90175-K","article-title":"Myelin proteolipid protein: minimum sequence requirements for active induction of autoimmune encephalomyelitis in SWR\/J and SJL\/J mice","volume":"39","author":"Tuohy","year":"1992","journal-title":"J Neuroimmunol"},{"key":"2023072508035855000_B3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1749-6632.1988.tb27093.x","article-title":"Experimental allergic encephalomyelitis mediated by murine encephalitogenic T-cell lines specific for myelin proteolipid apoprotein","volume":"540","author":"Satoh","year":"1988","journal-title":"Ann NY Acad Sci"},{"key":"2023072508035855000_B4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0165-5728(92)90016-E","article-title":"Induction of active and adoptive chronic-relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein","volume":"38","author":"McRae","year":"1992","journal-title":"J Neuroimmunol"},{"key":"2023072508035855000_B5","first-page":"162","article-title":"Homing to central nervous system vasculature by antigen-specific lymphocytes. 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