RGD Reference Report - PTPN22 controls virally-induced autoimmune diabetes by modulating cytotoxic T lymphocyte responses in an epitope-specific manner. - Rat Genome Database

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PTPN22 controls virally-induced autoimmune diabetes by modulating cytotoxic T lymphocyte responses in an epitope-specific manner.

Authors: Fousteri, G  Jofra, T  Di Fonte, R  Kuka, M  Iannacone, M  Battaglia, M 
Citation: Fousteri G, etal., Clin Immunol. 2015 Feb;156(2):98-108. doi: 10.1016/j.clim.2014.12.002. Epub 2014 Dec 13.
RGD ID: 11532754
Pubmed: PMID:25513733   (View Abstract at PubMed)
DOI: DOI:10.1016/j.clim.2014.12.002   (Journal Full-text)

Ptpn22 is one of the most potent autoimmunity predisposing genes and strongly associates with type 1 diabetes (T1D). Previous studies showed that non-obese diabetic mice with reduced expression levels of Ptpn22 are protected from T1D due to increased number of T regulatory (Treg) cells. We report that lack of Ptpn22 exacerbates virally-induced T1D in female rat insulin promoter lymphocytic choriomeningitis virus (RIP-LCMV-GP) mice, while maintaining higher number of Treg cells throughout the antiviral response in the blood and spleen but not in the pancreatic lymph nodes. GP33-41-specific pentamer-positive cytotoxic lymphocytes (CTLs) are numerically reduced in the absence of Ptpn22 at the expansion and contraction phase but reach wild-type levels at the memory phase. However, they show similar effector function and even a subtle increase in the production of IL-2. In contrast, NP396-404-specific CTLs develop normally at all phases but display enhanced effector function. Lack of Ptpn22 also augments the memory proinflammatory response of GP61-80 CD4 T cells. Hence, lack of Ptpn22 largely augments antiviral effector T cell responses, suggesting that caution should be taken when targeting Ptpn22 to treat autoimmune diseases where viral infections are considered environmental triggers.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTPN22Humantype 1 diabetes mellitus susceptibilityISOPtpn22 (Mus musculus) RGD 
Ptpn22Rattype 1 diabetes mellitus susceptibilityISOPtpn22 (Mus musculus) RGD 
Ptpn22Mousetype 1 diabetes mellitus susceptibilityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptpn22  (protein tyrosine phosphatase, non-receptor type 22)

Genes (Mus musculus)
Ptpn22  (protein tyrosine phosphatase, non-receptor type 22 (lymphoid))

Genes (Homo sapiens)
PTPN22  (protein tyrosine phosphatase non-receptor type 22)


Additional Information