GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288641/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288641GEOGSEfalsePTPMT1-dependent regulatory T cells mediate immunological tolerance to gut pathobiontsMitochondrial dysfunctions are emerging as key drivers of gut inflammation, colitis, and IBD, yet their role in regulating immune tolerance remains unclear. Meanwhile, pathobiont infections, such as those caused by Helicobacter species, affect nearly half the global population, with symptoms manifesting in only 20%, adding a new layer of complexity. The genetic and environmental factors that disrupt gut tolerogenic mechanisms, tipping the balance toward disease in symptomatic infections, are not fully understood. Here, we show that PTPMT1 impairs tolerance to Helicobacter via Treg cells, independently from T cell-generated Type I or Type II interferons. Without cardiolipin, Treg cells lose metabolic fitness and immunosuppressive potential, unleashing pro-inflammatory myeloid cells in the gut. As a result, PTPMT1 ΔT mice are highly vulnerable to pathobiont infections even without microbiome imbalance. Inflammation and helper T cell imbalance are conserved in Barth syndrome, linked to cardiolipin deficiency from TAFAZZIN mutations. Overall, we propose that T cell-specific PTPMT1 governs the balance between tolerance and inflammation in the gut, dictating outcomes in pathobiont infections.2026/04/01GSE288641GSM8771710GSM877171124247288641Mus musculus