Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity
Data files
Apr 15, 2024 version files 1.76 MB
Abstract
The 1858C>T allele of the tyrosine phosphatase PTPN22 is present in 5-10% of the North American population and is strongly associated with numerous autoimmune diseases. Although research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its pro-autoimmune allele have in anti-viral immunity remains poorly defined. Here, we use single-cell RNA-sequencing and functional studies to interrogate the impact of this pro-autoimmune allele on anti-viral immunity during Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13) infection. Mice homozygous for this allele (PEP-619WW) clear the LCMV-cl13 virus whereas wildtype (PEP-WT) mice cannot. This is associated with enhanced anti-viral CD4 T cell responses and a more immunostimulatory CD8a- cDC phenotype. Adoptive transfer studies demonstrated that PEP-619WW enhanced anti-viral CD4 T cell function through virus-specific CD4 T cell-intrinsic and extrinsic mechanisms. Taken together, our data show that the pro-autoimmune allele of Ptpn22 drives a beneficial anti-viral immune response thereby preventing what is normally a chronic virus infection.
These data demonstrate the mice expressing the autoimmunity-associated allele of PTPN22 (PEP-619WW) have improved clearance of LCMV-clone 13 and this is associated with an enhanced immune response in numerous immune cell types. This was shown through single-cell RNA sequencing, infection disease course studies, and functional analysis using adoptive transfers and flow cytometry. The Prism file contains information on all the raw data tables, statistical analysis, and the resulting graphs. There are 55 data tables.
Description of the data and file structure
The dataset contains raw data values, in Prism, for experiments listed in the publication. These datasets include weight loss values and survival for LCMV-clone13 infection studies, organ LCMV-clone13 titer data, and numerous files on quantifying different immune cell types, phenotypes, and functions derived from flow cytometry. Each data set file and graph file is labeled with a description of the experiment and correlates with the data presented in the manuscript. Analyses for each data set are also included. Single-cell RNA sequence raw data is not included in the dataset and is part of the GEO accession referenced in the manuscript.
- Ptpn22 1858C>T expressing mice labeled as PEP-619WW or PEP-WW or PEP-R619W
- Ptpn22 wildtype mice labeled as PEP-WT
- Ptpn22 knockout mice labeled as PEP-null or KO
- Abs. No. = Absolute Number
- PEP = PEST-domain Enriched Phosphatase
- LCMV-cl13 = Lymphocytic choriomeningitis virus clone 13
- Treg = T regulatory cell
- Dpi = days post-infection
- LCMV-NP = Lymphocytic choriomeningitis virus Nucleoprotein
- cDC = conventional Dendritic Cell
- pDC = plasmacytoid Dendritic Cell
- IFN-I = Type I Interferon
- Th1 = T Helper 1 cell
- TFH = T Follicular helper cell
- IFNg = Interferon-gamma
- TNFa = Tumor necrosis factor-alpha
- IL-2 = Interleukin 2
- GP = glycoprotein
- PD-L1 = Program death receptor ligand 1
- APC = antigen-presenting cell
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