ArticleJCI insight2020
PTPN2 links colonic and joint inflammation in experimental autoimmune arthritis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Inflammatory Bowel Disease-Associated Spondyloarthritis.Journal of clinical medicine · 2026Review
- Identifying Donor Immune Cells in the Intestinal Mucosa of Chimeric Recipient Mice by Immunofluorescence.Current protocols · 2026Article
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- From intestinal immune niches to systemic inflammation: programming cellular plasticity and immune redistribution across organs.Frontiers in immunology · 2026Review
- TScience immunology · 2025Article
- Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.Journal of autoimmunity · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Effect of Integrin Blockade on Experimental Spondyloarthritis.Biomolecules · 2024Article
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- ABCD of IA: A multi-scale agent-based model of T cell activation in inflammatory arthritis.Biomaterials science · 2024Article
- The therapeutic potential of immunoengineering for systemic autoimmunity.Nature reviews. Rheumatology · 2024Review
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Identification of human exTNature immunology · 2023Article
- Short-chain fatty acid-mediated epigenetic modulation of inflammatory T cells in vitro.Drug delivery and translational research · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- PTPN2 regulates bacterial clearance in a mouse model of enteropathogenic and enterohemorrhagic E. coli infection.JCI insight · 2023Article
- Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
Abstract
Loss-of-function variants of protein tyrosine phosphatase non-receptor type 2 (PTPN2) enhance risk of inflammatory bowel disease and rheumatoid arthritis; however, whether the association between PTPN2 and autoimmune arthritis depends on gut inflammation is unknown. Here we demonstrate that induction of subclinical intestinal inflammation exacerbates development of autoimmune arthritis in SKG mice. Ptpn2-haploinsufficient SKG mice - modeling human carriers of disease-associated variants of PTPN2 - displayed enhanced colitis-induced arthritis and joint accumulation of Tregs expressing RAR-related orphan receptor γT (RORγt) - a gut-enriched Treg subset that can undergo conversion into FoxP3-IL-17+ arthritogenic exTregs. SKG colonic Tregs underwent higher conversion into arthritogenic exTregs when compared with peripheral Tregs, which was exacerbated by haploinsufficiency of Ptpn2. Ptpn2 haploinsufficiency led to selective joint accumulation of RORγt-expressing Tregs expressing the colonic marker G protein-coupled receptor 15 (GPR15) in arthritic mice and selectively enhanced conversion of GPR15+ Tregs into exTregs in vitro and in vivo. Inducible Treg-specific haploinsufficiency of Ptpn2 enhanced colitis-induced SKG arthritis and led to specific joint accumulation of GPR15+ exTregs. Our data validate the SKG model for studies at the interface between intestinal and joint inflammation and suggest that arthritogenic variants of PTPN2 amplify the link between gut inflammation and arthritis through conversion of colonic Tregs into exTregs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.