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For example, SKG mice, which carry a hypomorphic point mutation of the Zap\u201070 gene, spontaneously develop T\u2010cell\u2013mediated autoimmune arthritis immunopathologically similar to human rheumatoid arthritis (RA). The Zap\u201070 mutation alters the sensitivity of developing T cells to thymic positive\/negative selection by self\u2010peptides\/MHC complexes, shifting self\u2010reactive TCR repertoire to include a dominant arthritogenic specificity and also affecting thymic development and function of autoimmune suppressive regulatory T (Treg) cells. Polyclonal self\u2010reactive T cells, including potentially arthritogenic T cells, thus produced by the thymus recognize self\u2010peptide\/MHC complexes on antigen\u2010presenting cells (APCs) in the periphery and stimulate them to produce cytokines including IL\u20106 to drive the arthritogenic T cells to differentiate into arthritogenic T\u2010helper 17 (Th17) cells. Insufficient Treg suppression or activation of APCs via microbial and other environmental stimuli evokes arthritis by activating granulocyte\u2010macrophage colony\u2010stimulating factor\u2010secreting effector Th17 cells, mediating chronic bone\u2010destructive joint inflammation by activating myeloid cells, innate lymphoid cells, and synoviocytes in the joint. These findings obtained from the study of SKG mouse arthritis are instrumental in understanding how arthritogenic T cells are produced, become activated, and differentiate into effector T cells mediating arthritis, and may help devising therapeutic measures targeting autoimmune pathogenic Th17 cells or autoimmune\u2010suppressing Treg cells to treat and prevent RA.<\/jats:p>","DOI":"10.1111\/imr.12841","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T11:06:04Z","timestamp":1579172764000},"page":"164-176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Impaired T cell receptor signaling and development of T cell\u2013mediated autoimmune arthritis"],"prefix":"10.1111","volume":"294","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-9524","authenticated-orcid":false,"given":"Yusuke","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Laboratory of Integrative 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