Abstract
PTPN22 encodes a tyrosine phosphatase that inhibits Src-family kinases responsible for Ag receptor signaling in lymphocytes and is strongly linked with susceptibility to a number of autoimmune diseases. As strength of TCR signal is critical to the thymic selection of regulatory T cells (Tregs), we examined the effect of murine PTPN22 deficiency on Treg development and function. In the thymus, numbers of pre-Tregs and Tregs increased inversely with the level of PTPN22. This increase in Tregs persisted in the periphery and could play a key part in the reduced severity observed in the PTPN22-deficient mice of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. This could explain the lack of association of certain autoimmune conditions with PTPN22 risk alleles.
Footnotes
This work was supported by Grants AI070351 and AI050864 from the National Institutes of Health. L.S.W. is supported by grants from the Juvenile Diabetes Research Foundation and the Wellcome Trust. The Cambridge Institute for Medical Research is the recipient of a Wellcome Trust Strategic Award (079895). N.B. is supported by National Institutes of Health Grant 5R01AI070544.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- cRPMI
- complete RPMI 1640
- EAE
- experimental autoimmune encephalomyelitis
- Het
- heterozygous (PTPN22+/−)
- KO
- knockout (PTPN22−/−)
- Lyp
- lymphoid tyrosine phosphatase
- MOG
- myelin oligodendrocyte protein
- Pep
- PEST-enriched protein tyrosine phosphatase
- qPCR
- quantitative real-time PCR
- T1D
- type 1 diabetes
- Teff
- T effector cell
- Treg
- regulatory T cell
- TSRI
- The Scripps Research Institute
- WT
- wild-type.
- Received January 12, 2012.
- Accepted March 23, 2012.
- Copyright © 2012 by The American Association of Immunologists, Inc.
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