Regulation of autoimmune and anti‐tumour T‐cell responses by PTPN22

Abstract

A number of polymorphisms in immune-regulatory genes have been identified as risk factors for the development of autoimmune disease. PTPN22 (that encodes a tyrosine phosphatase) has been associated with the development of several autoimmune diseases, including type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus. PTPN22 regulates the activity and effector functions of multiple important immune cell types, including lymphocytes, granulocytes and myeloid cells. In this review, we describe the role of PTPN22 in regulating T-cell activation and effector responses. We discuss progress in our understanding of the impact of PTPN22 in autoimmune disease in humans and mouse models, as well as recent evidence suggesting that genetic manipulation of PTPN22 expression might enhance the efficacy of anti-tumour T-cell responses.

Association of common type 1 and type 2 diabetes gene variants with latent autoimmune diabetes in adults: A meta‐analysis

“…This gene plays an important role in controlling the activity of various immune cells, especially B and T cells. Several studies have demonstrated an association between PTPN22 polymorphisms and the risk of T1D and other autoimmune diseases . However, the association of PTPN22 with LADA has not been widely explored.…”

Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non‐coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem)

“…The PTPN22 gene encodes the lymphoid phosphatase LYP (or PTPN22) that belongs to the protein tyrosine phosphatases (PTP) family and regulates the activity and effector functions of multiple immune cell types (Brownlie, Zamoyska, & Salmond, ). An additional gene located in the 1p13.2 region is RSBN1, whose ortholog in the mouse, Rsbn1 (also named Rosbin or KDM9), has been shown to encode the lysine‐specific histone demethylase 9 that specifically demethylates the dimethylated lysine 20 of histone H4 (H4K20me2), thereby modulating chromosome architecture (Brejc et al., ).…”

PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients

“…The protein tyrosine phosphatase non‐receptor type 22 gene ( PTPN22 ) encodes the lymphoid protein tyrosine phosphatase LYP, which is expressed exclusively in hematopoietic cells, including T and B cells . LYP is a potent negative regulator of T and B lymphocyte activation by modulating T‐cell receptor (TCR) and B‐cell receptor (BCR) signaling …”

“…In addition, overexpression of CD154 on T cells correlates with higher RA activity . To date, the functional role of the PTPN22 1858C>T polymorphism in autoimmune diseases is not entirely clear and its precise impact on signaling pathways is highly context dependent . Since the CD40/CD154 interaction promotes B‐ and T‐cell activation and cytokine secretion, the aim of this study was to evaluate the relationship between the 1858 T risk allele with CD40 and CD154 expression and IFN‐γ secretion in anti‐CCP‐positive RA patients.…”

“…2 LYP is a potent negative regulator of T and B lymphocyte activation by modulating T-cell receptor (TCR) and B-cell receptor (BCR) signaling. [3][4][5][6] A functional single nucleotide polymorphism (SNP) 1858C>T (rs2476601) in the PTPN22 gene leads to the 620Arg>Trp substitution within the first pro-rich region in the C-terminus of LYP and has been consistently associated with RA susceptibility and anti-CCP antibodies seropositivity. [7][8][9] In the western Mexican population, this polymorphism has been found in low frequency (1858 T allele, 6%), however, it has been consistently associated with RA risk.…”