Research ArticleAUTOIMMUNITY

PTPN22 inhibition resets defective human central B cell tolerance

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Science Immunology  22 Jul 2016:
Vol. 1, Issue 1, pp. aaf7153
DOI: 10.1126/sciimmunol.aaf7153

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Restoring tolerance

Therapies that target and eliminate B cells have had some success in patients with autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. However, restoring tolerance in self-reactive B cells that lead to disease remains an unmet goal. The 1858T allele of protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) has been associated with autoreactive B cells in autoimmune disease in humans. Now, Schickel et al. report that this allele interferes with the development of central B cell tolerance in a humanized mouse model of autoimmunity and that blocking PTPN22 can restore this defect. If these observations hold true in humans, targeting PTPN22 may be able to restore B cell tolerance in patients with autoimmune disease.