title: Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease.
abstract: Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple sclerosis (MS). The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of TH17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred TH17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of TH17 cells in the gut was partially dependent on the gut homing receptor α4β7-mediated adhesion to the intestine. Administration of α4β7 blocking-antibodies increased the peripheral availability of TH17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.
authors: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
authors: Kerstin
authors: K
authors: Berer
authors: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
authors: Marina
authors: M
authors: Boziki
authors: Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
authors: Gurumoorthy
authors: G
authors: Krishnamoorthy
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016023:Integrins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D016023:Integrins; D063308:Myelin-Oligodendrocyte Glycoprotein; D011948:Receptors, Antigen, T-Cell; C071777:integrin alpha4beta7