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Lack of the Phosphatase PTPN22 Increases Adhesion of Murine Regulatory T Cells to Improve Their Immunosuppressive Function

Brownlie, Rebecca J.; Miosge, Lisa A.; Vassilakos, Demetrios; Svensson, Lena M LU ; Cope, Andrew and Zamoyska, Rose (2012) In Science Signaling 5(252). p.87-87
Abstract
The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; however, the precise function of PTPN22 and how mutations contribute to auto-immunity remain controversial. Loss-of-function mutations in PTPN22 are associated with increased numbers of effector T cells and autoreactive B cells in humans and mice; however, the complete absence of PTPN22 in mice does not result in spontaneous autoimmunity. We found that PTPN22 was a key regulator of regulatory T cell (T-reg) function that... (More)
The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; however, the precise function of PTPN22 and how mutations contribute to auto-immunity remain controversial. Loss-of-function mutations in PTPN22 are associated with increased numbers of effector T cells and autoreactive B cells in humans and mice; however, the complete absence of PTPN22 in mice does not result in spontaneous autoimmunity. We found that PTPN22 was a key regulator of regulatory T cell (T-reg) function that fine-tuned the signaling of the T cell receptor and integrins. PTPN22(-/-) T-regs were more effective at immunosuppression than were wild-type T-regs, and they suppressed the activity of PTPN22(-/-) effector T cells, preventing autoimmunity. Compared to wildtype T-regs, PTPN22(-/-) T-regs produced increased amounts of the immunosuppressive cytokine interleukin-10 and had enhanced adhesive properties mediated by the integrin lymphocyte function-associated antigen-1, processes that are critical for T-reg function. This previously undiscovered role of PTPN22 in regulating integrin signaling and T-reg function suggests that PTPN22 may be a useful therapeutic target for manipulating T-reg function in human disease. (Less)
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type
Contribution to journal
publication status
published
subject
in
Science Signaling
volume
5
issue
252
pages
87 - 87
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • wos:000311749700005
  • scopus:84870318487
ISSN
1937-9145
DOI
10.1126/scisignal.2003365
language
English
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yes
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ae80fc91-0a59-4ab3-8245-b6406fa53fe8 (old id 3372796)
date added to LUP
2013-02-01 07:01:23
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2017-10-29 03:22:56
@article{ae80fc91-0a59-4ab3-8245-b6406fa53fe8,
  abstract     = {The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; however, the precise function of PTPN22 and how mutations contribute to auto-immunity remain controversial. Loss-of-function mutations in PTPN22 are associated with increased numbers of effector T cells and autoreactive B cells in humans and mice; however, the complete absence of PTPN22 in mice does not result in spontaneous autoimmunity. We found that PTPN22 was a key regulator of regulatory T cell (T-reg) function that fine-tuned the signaling of the T cell receptor and integrins. PTPN22(-/-) T-regs were more effective at immunosuppression than were wild-type T-regs, and they suppressed the activity of PTPN22(-/-) effector T cells, preventing autoimmunity. Compared to wildtype T-regs, PTPN22(-/-) T-regs produced increased amounts of the immunosuppressive cytokine interleukin-10 and had enhanced adhesive properties mediated by the integrin lymphocyte function-associated antigen-1, processes that are critical for T-reg function. This previously undiscovered role of PTPN22 in regulating integrin signaling and T-reg function suggests that PTPN22 may be a useful therapeutic target for manipulating T-reg function in human disease.},
  author       = {Brownlie, Rebecca J. and Miosge, Lisa A. and Vassilakos, Demetrios and Svensson, Lena M and Cope, Andrew and Zamoyska, Rose},
  issn         = {1937-9145},
  language     = {eng},
  number       = {252},
  pages        = {87--87},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Signaling},
  title        = {Lack of the Phosphatase PTPN22 Increases Adhesion of Murine Regulatory T Cells to Improve Their Immunosuppressive Function},
  url          = {http://dx.doi.org/10.1126/scisignal.2003365},
  volume       = {5},
  year         = {2012},
}