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T‐cell receptor signaling and the pathogenesis of autoimmune arthritis: insights from mouse and man
Author(s) -
Sakaguchi Shimon,
Benham Helen,
Cope Andrew P,
Thomas Ranjeny
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2012.4
Subject(s) - autoimmunity , t cell receptor , major histocompatibility complex , biology , immune system , immunology , signal transduction , t cell , acquired immune system , microbiology and biotechnology , arthritis , innate immune system , antigen , neuroscience
The immune system has evolved to survey and respond appropriately to the universe of foreign pathogens, while at the same time deploying an intricate repertoire of mechanisms that keep responses to host tissues in check. For the adaptive immune system, specificity and sensitivity are provided by a large repertoire of antigen T‐cell receptors (TCRs) constructed in their extracellular domain to recognize antigenic peptide fragments restricted and presented by histocompatibility complex molecules, and coupled through intracellular domains to signal transduction modules that serve to transmit environmental cues inside the cell. In this review we consider recent evidence that has provided insight into how altered TCR signaling thresholds could contribute to human autoimmune arthritis, including rheumatoid arthritis (RA), and the spondyloarthropathies (SpA). We also discuss mechanistic studies that demonstrate how perturbations of T‐cell antigen receptor signaling in the SKG mouse model can promote systemic autoimmunity and the intersection with essential innate immune pathways that lead to the development of chronic inflammatory phenotypes.