Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis.
Because presentation of acetylcholine receptor (AChR) peptides to T cells is critical to the development of myasthenia gravis, we examined the role of cathepsin S (Cat S) in experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. Compared with wild type, Cat S null mice were markedly resistant to the development of EAMG, and showed reduced T and B cell responses to AChR. Cat S null mice immunized with immunodominant AChR peptides showed weak responses, indicating failed peptide presentation accounted for autoimmune resistance. A Cat S inhibitor suppressed in vitro IFN-gamma production by lymph node cells from AChR-immunized, DR3-bearing transgenic mice. Because Cat S null mice are not severely immunocompromised, Cat S inhibitors could be tested for their therapeutic potential in EAMG.
Yang
Huan
H
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Kala
Mrinalini
M
Scott
Benjamin G
BG
Goluszko
Elzbieta
E
Chapman
Harold A
HA
Christadoss
Premkumar
P
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000473:pathology; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014101:Torpedo
D001323:Autoantibodies; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015803:HLA-DR3 Antigen; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D002403:Cathepsins; C028217:cathepsin S