Resident cutaneous memory T cells: a clinical review of their role in chronic inflammatory dermatoses and potential as therapeutic targets

Resident memory T cells (T-RMs) remain in epithelial barrier tissues after antigen exposure and the initial effector phase. These T-RMs provide effective antimicrobial and anticancer immunity; however, pathogenic T-RMs have been shown to mediate various chronic inflammatory disorders in a variety of tissue types. In the skin, T-RMs are referred to as resident cutaneous memory T cells (cT-RMs). Understanding the mechanisms leading to the development and establishment of these cT-RMs populations may allow for targeted treatments that provide durable responses in chronic immune-mediated skin diseases, even after cessation. In this review, we summarize the evidence on cT-RMs as drivers of chronic inflammatory dermatoses, including psoriasis, vitiligo, atopic dermatitis, cutaneous lupus erythematosus and alopecia areata, among others. Data from in vitro, animal model and ex vivo human studies are presented, with a focus on the potential for cT-RMs to trigger acute disease flares, as well as recurrent disease, by establishing an immune 'memory' in the skin. Furthermore, the available data on the potential for existing and novel treatments to affect the development or survival of cT-RMs in the skin are synthesized. The data suggest a dynamic and rapidly growing area in the field of dermatology; however, we also discuss areas in need of greater research to allow for optimal treatment selection for long-term disease control.