title: Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice.
abstract: MRL/Mp-Fas (lpr) (MRL-lpr) mice develop a systemic autoimmune disease and are considered to be a good model for systemic lupus erythematosus in humans. We have recently shown that mice lacking B and T lymphocyte attenuator (BTLA), an inhibitory co-receptor expressed mainly on lymphocytes, on a 129SvEv background spontaneously develop lymphocytic infiltration in multiple organs and an autoimmune hepatitis (AIH)-like disease. In this study, we investigated the role of BTLA in the pathogenesis of autoimmune diseases in MRL-lpr mice. We found that BTLA-deficient (BTLA(-/-)) MRL-lpr/lpr mice developed severe lymphocytic infiltration in salivary glands, lungs, pancreas, kidneys and joints as compared with BTLA-sufficient (BTLA(+/+)) MRL-lpr/lpr mice. In addition, although AIH-like disease was not found in BTLA(+/+) MRL-lpr/lpr mice, AIH-like disease was exacerbated in BTLA(-/-) MRL-lpr/lpr mice as compared with that in BTLA(-/-) 129SvEv mice. These results suggest that BTLA plays a protective role in autoimmune diseases in MRL-lpr mice and that AIH-like disease develops in BTLA(-/-) mice even in the absence of Fas-dependent signaling.
authors.affiliation: Department of Allergy and Clinical Immunology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oya
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Owada
authors.forename: Mie
authors.initials: M
authors.lastname: Oki
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kagami
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D053222:Fas Ligand Protein / Q000378:metabolism*; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*
chemical_list: C488868:BTLA protein, mouse; D053222:Fas Ligand Protein; D011971:Receptors, Immunologic