Tissue Resident Memory Cells: Friend or Foe?

Abstract

Tissue-resident memory T (T_RM) cells are a specialised subset of immune cells that remain within tissues, playing a vital role in localised immune defence and long-term immunity. Unlike circulating memory T cells, T_RM cells do not recirculate to provide rapid and effective responses against previously encountered pathogens at the tissue level. The formation of T_RM cells is driven by tissue-specific cues, guiding their differentiation and retention within organs such as the skin, lungs and gut. They are characterised by the expression of unique markers, including CD69 and CD103, which facilitate their retention and longevity in tissues. T_RM cells are essential for immune surveillance, effectively detecting and responding to different infections and contributing to tumour suppression. However, T_RM cells are also implicated in chronic inflammatory and autoimmune diseases, where persistent activation by resident and autoantigens can lead to tissue damage. This pathogenic role is evident in chronic inflammatory conditions such as psoriasis, vitiligo and inflammatory bowel disease (IBD), where T_RM cells may drive persistent localised inflammation and contribute to disease progression and severity. Emerging therapeutic strategies seek to modulate T_RM cells to balance their protective and pathogenic roles in these inflammatory diseases. Approaches such as checkpoint inhibitors, cytokine modulation and cell-depletion therapies aim to enhance T_RM cells' beneficial immune functions while minimising their role in autoimmunity. A deeper understanding of T_RM cell development, maintenance and functional diversity is critical for advancing treatments for infectious diseases, chronic inflammation, autoimmune conditions and cancer.