Scholarlink

<p>Feline chronic gingivostomatitis (FCGS) is a debilitating oral disease characterized by immune dysregulation and chronic inflammation. We hypothesized that CD8 + T cells from FCGS cats exhibit exhaustion features with suppressed mitochondrial pathways, and that mesenchymal stromal cell (MSC) therapy post-extractions might restore these programs. RNA sequencing was performed on peripheral CD8 + T cells from cats with active FCGS before (disease group, D) and after (treated group, M) clinical remission following full-mouth extractions and MSC therapy, with specific-pathogen-free cats as controls (control group, C). CD8 + T cells from active disease displayed terminal effector differentiation and exhaustion-like signatures, including upregulation of cytotoxic markers (GZMB, GZMK, GZMA), differentiation markers (KLRG1, IL18R1/IL18RAP), and exhaustion-associated genes (EOMES, CD244, TNFSF10, CCR5, PRDM1, RGS16). Gene set enrichment analysis confirmed exhaustion-like CD8 + T-cell phenotype enrichment in active disease, which resolved after treatment. Pathway analysis revealed marked downregulation of mitochondrial respiratory chain components, ATP synthesis, and protein import pathways in active FCGS, with partial post-treatment resolution. Immunofluorescence of draining lymph nodes showed significantly increased CTLA-4 + CD3+ T cells in both FCGS groups versus controls, suggesting persistent immunoregulatory signaling despite clinical improvement. These findings identify overlapping T-cell exhaustion and mitochondrial dysfunction-associated transcriptomic signatures in FCGS, supporting therapeutic strategies targeting immune-metabolic pathways.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Transcriptomic evidence of CD8⁺ T-cell exhaustion-like phenotype and mitochondrial impairment underlying immune dysregulation in feline chronic gingivostomatitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月6日

查看全文
  • Maria Soltero-Rivera,
  • Patrawin Wanakumjorn,
  • Yihong Chen,
  • Samantha Barnum,
  • Luis Diego Castillo Charpentier,
  • Boaz Arzi,
  • Natalia Vapniarsky Arzi,
  • Amir Kol

摘要

Feline chronic gingivostomatitis (FCGS) is a debilitating oral disease characterized by immune dysregulation and chronic inflammation. We hypothesized that CD8 + T cells from FCGS cats exhibit exhaustion features with suppressed mitochondrial pathways, and that mesenchymal stromal cell (MSC) therapy post-extractions might restore these programs. RNA sequencing was performed on peripheral CD8 + T cells from cats with active FCGS before (disease group, D) and after (treated group, M) clinical remission following full-mouth extractions and MSC therapy, with specific-pathogen-free cats as controls (control group, C). CD8 + T cells from active disease displayed terminal effector differentiation and exhaustion-like signatures, including upregulation of cytotoxic markers (GZMB, GZMK, GZMA), differentiation markers (KLRG1, IL18R1/IL18RAP), and exhaustion-associated genes (EOMES, CD244, TNFSF10, CCR5, PRDM1, RGS16). Gene set enrichment analysis confirmed exhaustion-like CD8 + T-cell phenotype enrichment in active disease, which resolved after treatment. Pathway analysis revealed marked downregulation of mitochondrial respiratory chain components, ATP synthesis, and protein import pathways in active FCGS, with partial post-treatment resolution. Immunofluorescence of draining lymph nodes showed significantly increased CTLA-4 + CD3+ T cells in both FCGS groups versus controls, suggesting persistent immunoregulatory signaling despite clinical improvement. These findings identify overlapping T-cell exhaustion and mitochondrial dysfunction-associated transcriptomic signatures in FCGS, supporting therapeutic strategies targeting immune-metabolic pathways.