Tissue-Resident Memory T Cells in Rheumatoid Immune Diseases: Pathogenic Mechanisms and Therapeutic Strategies

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Tissue-resident memory T (T_RM) cells provide local immunity but also drive chronic inflammation in rheumatoid immune diseases.
• Emerging evidence implicates T_RM cells in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and primary Sjögren's syndrome (pSS).

Purpose of the Study:

• To review the fundamental biology, pathogenic roles, and therapeutic modulation of T_RM cells in autoimmune diseases.
• To highlight disease-specific mechanisms and evaluate current and future therapeutic strategies targeting T_RM cells.

Main Methods:

• Systematic literature search of PubMed, Web of Science, and Google Scholar (through October 2025).
• Review and synthesis of studies on T_RM cell biology, pathogenesis, and therapeutic interventions in autoimmune conditions.

Main Results:

• T_RM cells exhibit TGF-β and IL-15 dependent development, tissue-specific heterogeneity, and unique metabolic programs.
• Disease-specific roles include promoting osteoclastogenesis in RA, amplifying type I interferon responses in SLE, contributing to fibrosis in SSc, and mediating glandular injury in pSS.
• Therapeutic strategies include JAK inhibitors, IL-17/IL-23 blockade, and nanotechnology-based interventions, though challenges in tissue-specific targeting persist.

Conclusions:

• Targeting T_RM cells is a promising strategy for achieving long-term remission in rheumatoid immune diseases.
• Future research directions include spatial transcriptomics, organoid models, and AI for precision medicine approaches.
• Developing tissue-specific targeting strategies is crucial for efficacy without compromising systemic immunity.