PMID- 12594253 OWN - NLM STAT- MEDLINE DCOM- 20030521 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 170 IP - 5 DP - 2003 Mar 1 TI - Induction of low dose oral tolerance in monocyte chemoattractant protein-1- and CCR2-deficient mice. PG - 2316-22 AB - The chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 have been shown to play an important role in the migration and trafficking of macrophages and Th1 effector cells in experimental autoimmune encephalomyelitis. Also, MCP-1 has been reported to regulate oral tolerance induction by inhibition of Th1 cell-related cytokines and by the ability of Abs to MCP-1 to inhibit oral tolerance. This study demonstrates that neither MCP-1 nor its receptor CCR2 is required for the induction of oral tolerance. Mice deletional for either MCP-1 or CCR2 had suppressed cell-proliferative and Th1 responses following oral administration and immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)). TGF-beta was up-regulated in fed and immunized deletional mice, while IL-4 was absent from deletional mice, but up-regulated in controls. Decreased experimental autoimmune encephalomyelitis severity was found in MOG(35-55)-fed MCP-1 deletional mice, indicating induction of oral tolerance. These results demonstrate that MCP-1 is not required for induction of oral tolerance and that MCP-1 and CCR2 are essential for up-regulation of IL-4 in tolerized mice. FAU - Gonnella, Patricia A AU - Gonnella PA AD - Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. patricia.gonnella@tch.harvard.edu FAU - Kodali, Dhatri AU - Kodali D FAU - Weiner, Howard L AU - Weiner HL LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Glycoproteins) RN - 0 (Myelin-Oligodendrocyte Glycoprotein) RN - 0 (Peptide Fragments) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (myelin oligodendrocyte glycoprotein (35-55)) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Administration, Oral MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/*deficiency/*genetics/metabolism MH - Dose-Response Relationship, Immunologic MH - Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/pathology MH - Female MH - Glycoproteins/administration & dosage/immunology MH - Immune Tolerance/*genetics MH - Immunohistochemistry MH - Injections, Subcutaneous MH - Interleukin-4/biosynthesis MH - Intestinal Mucosa/chemistry/immunology/metabolism MH - Intubation, Gastrointestinal MH - Lymphoid Tissue/chemistry/immunology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myelin-Oligodendrocyte Glycoprotein MH - Peptide Fragments/administration & dosage/immunology MH - Receptors, CCR2 MH - Receptors, Chemokine/*deficiency/*genetics MH - Up-Regulation/genetics/immunology EDAT- 2003/02/21 04:00 MHDA- 2003/05/22 05:00 CRDT- 2003/02/21 04:00 PHST- 2003/02/21 04:00 [pubmed] PHST- 2003/05/22 05:00 [medline] PHST- 2003/02/21 04:00 [entrez] AID - 10.4049/jimmunol.170.5.2316 [doi] PST - ppublish SO - J Immunol. 2003 Mar 1;170(5):2316-22. doi: 10.4049/jimmunol.170.5.2316.