The protein tyrosine phosphatase PTPN22 negatively regulates presentation of immune complex derived antigens.
The protein tyrosine phosphatase PTPN22 negatively regulates presentation of immune complex derived antigens.
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DOI：
10.1038/s41598-018-31179-x
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发表时间：
2018-08-23
影响因子：
4.6
通讯作者：
Cope AP
中科院分区：
文献类型：
--
作者：
Clarke F;Purvis HA;Sanchez-Blanco C;Gutiérrez-Martinez E;Cornish GH;Zamoyska R;Guermonprez P;Cope AP
PTPN 22内的C1858 T单核苷酸多态性（编码PTPN 22 R620 W）与多种自身免疫性疾病（包括1型糖尿病和类风湿性关节炎）的易感性增强相关。许多相关的自身免疫性疾病都有自身抗体的病理成分。Fc受体（FcR）在自身抗体与自身抗原结合并形成免疫复合物时识别自身抗体。在免疫复合物结合和受体交联后，FcR通过Src和Syk家族激酶发出信号，导致抗原摄取、呈递和细胞因子分泌。Ptpn 22编码蛋白酪氨酸磷酸酶，其负调节邻近免疫受体信号级联的Src和Syk家族激酶。因此，我们假设PTPN 22调节树突状细胞（DC）中免疫复合物刺激的FcR应答。将来自野生型（WT）或Ptpn 22-/-小鼠的骨髓来源的DC（BMDC）用卵清蛋白：抗卵清蛋白免疫复合物（ova IC）脉冲。与WT OT-II T细胞的共培养揭示了ova IC脉冲的Ptpn 22 −/− BMDC具有增强的诱导T细胞增殖的能力。这与Ptpn 22 −/− BMDC呈递免疫复合物衍生抗原和形成卵IC依赖性DC-T细胞缀合物的能力增加有关。这些发现突出了PTPN 22作为FcR介导的应答的调节剂，并提供了PTPN 22 R620 W与自身抗体相关的自身免疫性疾病之间的联系。
A C1858T single nucleotide polymorphism within PTPN22 (which encodes PTPN22R620W) 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 PTPN22R620W with autoantibody associated autoimmune diseases.
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Fcgamma受体介导的巨噬细胞中缺乏SRC家族酪氨酸激酶HCK，FGR和Lyn的吞噬作用。
影响因子：
15.3
作者：
Fitzer-Attas, C J;Lowry, M;Crowley, M T;Finn, A J;Meng, F;DeFranco, A L;Lowell, C A
通讯作者：
Lowell, C A
影响因子：
3.7
作者：
Clarke F;Jordan CK;Gutiérrez-Martinez E;Bibby JA;Sanchez-Blanco C;Cornish GH;Dai X;Rawlings DJ;Zamoyska R;Guermonprez P;Cope AP;Purvis HA
通讯作者：
Purvis HA
影响因子：
9.8
作者：
Kyogoku, C;Langefeld, CD;Behrens, TW
通讯作者：
Behrens, TW
DOI：
10.1084/jem.186.7.1027
发表时间：
1997-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Crowley MT;Costello PS;Fitzer-Attas CJ;Turner M;Meng F;Lowell C;Tybulewicz VL;DeFranco AL
通讯作者：
DeFranco AL
影响因子：
3.3
作者：
Le Roux, Delphine;Lankar, Danielle;Lennon-Dumenil, Ana-Maria
通讯作者：
Lennon-Dumenil, Ana-Maria