The protein tyrosine phosphatase PTPN22 negatively regulates presentation of immune complex derived antigens

被引：19
作者：
Clarke, Fiona [1 ]
Purvis, Harriet A. [1 ]
Sanchez-Blanco, Cristina [1 ]
Gutierrez-Martinez, Enrique [1 ]
Cornish, Georgina H. [1 ]
Zamoyska, Rose [2 ]
Guermonprez, Pierre [1 ]
Cope, Andrew P. [1 ]
机构：
[1] Kings Coll London, Fac Life Sci & Med, Sch Immunol & Microbial Sci, Ctr Inflammat Biol & Canc Immunol, London SE1 1UL, England
[2] Univ Edinburgh, Ctr Immun Infect & Evolut, Inst Immunol & Infect Res, Edinburgh EH9 3FL, Midlothian, Scotland
来源：
SCIENTIFIC REPORTS | 2018年 / 8卷
基金：
英国生物技术与生命科学研究理事会;
关键词：
FC-GAMMA RECEPTORS; SINGLE-NUCLEOTIDE POLYMORPHISM; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS; GENETIC ASSOCIATION; VARIANT; AUTOIMMUNITY; SUSCEPTIBILITY; ACTIVATION; KINASE;
D O I：
10.1038/s41598-018-31179-x
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A C1858T single nucleotide polymorphism within PTPN22 (which encodes PTPN22(R620W)) is associated with an enhanced susceptibility to multiple autoimmune diseases including type 1 diabetes and rheumatoid arthritis. Many of the associated autoimmune diseases have an autoantibody component to their pathology. Fc receptors (FcRs) recognise autoantibodies when they bind to autoantigens and form immune complexes. After immune complex binding and receptor crosslinking, FcRs signal via Src and Syk family kinases, leading to antigen uptake, presentation and cytokine secretion. Ptpn22 encodes a protein tyrosine phosphatase that negatively regulates Src and Syk family kinases proximal to immunoreceptor signalling cascades. We therefore hypothesised that PTPN22 regulates immune complex stimulated FcR responses in dendritic cells (DCs). Bone marrow derived DCs (BMDCs) from wild type (WT) or Ptpn22(-/-) mice were pulsed with ovalbumin: anti-ovalbumin immune complexes (ova ICs). Co-culture with WT OT-II T cells revealed that ova IC pulsed Ptpn22(-/-) BMDCs have an enhanced capability to induce T cell proliferation. This was associated with an increased capability of Ptpn22(-/-) BMDCs to present immune complex derived antigens and to form ova IC dependent DC-T cell conjugates. These findings highlight PTPN22 as a regulator of FcR mediated responses and provide a link between the association of PTPN22(R620W) with autoantibody associated autoimmune diseases.
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页数：11
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