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

Scientific Reports
Fiona ClarkeAndrew P Cope

Abstract

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 depend...Continue Reading

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Citations

Apr 17, 2019·Nature Communications·Manuel A FerreiraGeorgia Chenevix-Trench
Jul 29, 2020·Frontiers in Immunology·Fabian JunkerOmar Qureshi
Feb 3, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Peter L ToogoodDavid Hoffman
Feb 20, 2021·Frontiers in Immunology·Matthew ClarkRoland M Tisch
Oct 8, 2021·FEBS Letters·David MillrineSimon A Jones

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Methods Mentioned

BETA
PMA
flow cytometry
FACS

Software Mentioned

TreeStar
FACS Diva
Flowjo
Prism
GraphPad

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