Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1.
A point mutation of the gene encoding ZAP-70, a key signal transduction molecule in T cells, results in spontaneous development of T cell-mediated autoimmune arthritis in mice homozygous for the mutation. The genetic anomaly alters differentiation and selection of T cells in the thymus, leading to thymic production of arthritogenic autoimmune T cells. The arthritogenic T cells persist in the periphery and elicit arthritis when activated by microbial agents that stimulate innate immunity. This model is instrumental in understanding how genetic variations in T cell signal transduction, together with environmental influences, contribute to the development of autoimmune disease.
Sakaguchi
Shimon
S
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. shimon@frontier.kyoto-u.ac.jp
Sakaguchi
Noriko
N
Yoshitomi
Hiroyuki
H
Hata
Hiroshi
H
Takahashi
Takeshi
T
Nomura
Takashi
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
D051746:ZAP-70 Protein-Tyrosine Kinase