title: H(1)R expression by CD11B(+) cells is not required for susceptibility to experimental allergic encephalomyelitis.
abstract: The histamine H(1) receptor (Hrh1/H(1)R) was identified as an autoimmune disease gene in experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS). Previously, we showed that selective re-expression of H(1)R by endothelial cells or T cells in H(1)RKO mice significantly reduced or complemented EAE severity and cytokine responses, respectively. H(1)R regulates innate immune cells, which in turn influences peripheral and central nervous system CD4(+) T cell effector responses. Therefore, we selectively re-expressed H(1)R in CD11b(+) cells of H(1)RKO mice to test the hypothesis that H(1)R signaling in these cells contributes to EAE susceptibility. We demonstrate that transgenic re-expression of H(1)R by H(1)RKO-CD11b(+) cells neither complements EAE susceptibility nor T cell cytokine responses highlighting the cell-specific effects of Hrh1 in the pathogenesis of EAE and MS, and the need for cell-specific targeting in optimizing therapeutic interventions based on such genes.
authors.affiliation: Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Naresha
authors.initials: N
authors.lastname: Saligrama
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Noubade
authors.forename: Laure K
authors.initials: LK
authors.lastname: Case
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Cory
authors.initials: C
authors.lastname: Teuscher
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity; D011969:Receptors, Histamine H1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D016207:Cytokines; D011969:Receptors, Histamine H1