Lack of the Phosphatase PTPN22 Increases Adhesion of Murine Regulatory T Cells to Improve Their Immunosuppressive Function
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3372796
- author
- Brownlie, Rebecca J. ; Miosge, Lisa A. ; Vassilakos, Demetrios ; Svensson, Lena M LU ; Cope, Andrew and Zamoyska, Rose
- organization
- publishing date
- 2012
- 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
- pmid:23193160
- ISSN
- 1937-9145
- DOI
- 10.1126/scisignal.2003365
- language
- English
- LU publication?
- yes
- id
- ae80fc91-0a59-4ab3-8245-b6406fa53fe8 (old id 3372796)
- date added to LUP
- 2016-04-01 11:13:38
- date last changed
- 2022-04-20 18:02:02
@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}},
doi = {{10.1126/scisignal.2003365}},
volume = {{5}},
year = {{2012}},
}