Lack of acetylcholine nicotine alpha 7 receptor suppresses development of collagen-induced arthritis and adaptive immunity.
Activation of the alpha7 receptor (α7nAChR) has been shown to be important in inflammation and immune regulation, and is also essential in the neural cholinergic anti-inflammatory pathway. The aim of this study was to investigate the role of α7nAChR in the development of experimental arthritis and immune activation. Mice lacking the α7nAChR were immunized with collagen II and the development of arthritis was assessed. Another group of α7nAChR-deficient mice was immunized with ovalbumin, spleen and lymph node cells were isolated and the proliferative responses to restimulation with ovalbumin or concanavalin A were investigated. We could demonstrate significantly milder arthritis and less cartilage destruction, together with a decrease of T cell content in lymph nodes in mice lacking the α7nAChR compared to wild-type controls. In addition, mice lacking the α7nAChR had a deficient proliferative response to concanavalin A, whereas antigen presentation-dependent proliferation was not affected. These results indicate important roles for α7nAChR in arthritis development as well as in regulation of T cell-dependent immunological mechanisms. In addition, the data implicate α7nAChR as a therapeutic target for modulation of adaptive immune responses.
Westman
M
M
Karolinska Institute, Department of Medicine, Unit of Rheumatology, CMM:04, Karolinska University Hospital, Stockholm, Sweden.
Saha
S
S
Morshed
M
M
Lampa
J
J
D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D008934:Mitogens; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003208:Concanavalin A; D010047:Ovalbumin