The Translational Relevance of Human Circulating Memory Cutaneous Lymphocyte-Associated Antigen Positive T Cells in Inflammatory Skin Disorders

Abstract

Circulating memory T cells are heterogeneous in their tissue tropism. The skin-seeking T cell subset expresses the cutaneous lymphocyte-associated antigen (CLA) on their surface. CLA⁺ memory T cells not only migrate from blood to skin but also recirculate between blood and skin. Studying CLA⁺ memory T cells in cutaneous diseases has allowed a better understanding of immune-inflammatory mechanisms that take place. The analysis of the phenotypical features of these cells, their antigen specificity, cytokine production profile, and changes in relationship to clinical status and therapies among other characteristics have led to the concept that they constitute peripheral cellular biomarkers in T cell-mediated cutaneous conditions. CLA⁺ memory T cells are of relevance in the pathogenesis of several cutaneous diseases, such as psoriasis (PSO), atopic dermatitis, vitiligo, and drug-induced allergic reactions, to name a few. The interaction of circulating CLA⁺ T cells with skin-resident cells has been investigated in different ex vivo coculture models made out of clinical samples. Interestingly, microbes that are present in the skin or related with human skin diseases are preferentially recognized by CLA⁺ T cells. Thus, the interaction of Streptococcus pyogenes with CLA⁺ T cells in PSO is providing novel concepts that help to understand disease immunopathogenesis. The goal of this review is to present latest results in the field of CLA⁺ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology.

Keywords: CLA+ T cell; cutaneous inflammation; human; immunodermatology; skin-homing lymphocytes; translational.

Figure 1

Translational relevance of human circulating memory CLA⁺ T cells in inflammatory skin disorders. (A) In skin-draining lymph nodes, antigen-specific Langerhans cells encounter naïve T cells generating memory T cells that express the skin-homing receptor CLA. CLA⁺ memory T cells enter the general circulation, through efferent lymphatic vessels, and will extravase to inflamed skin. Some CLA⁺ memory T cells leave cutaneous tissue through afferent lymphatic vessels, Recirculating back to the bloodstream, whereas, others are retained at the epidermal layer as resident memory T cells. (B) Principal antigen/allergen/autoantigen-induced effector functions of CLA⁺ memory T cells in human inflammatory cutaneous conditions. AA, alopecia areata; ACD, allergic contact dermatitis; AD, atopic dermatitis; CLA, cutaneous-associated lymphoid antigen; CLP, cutaneous lichen planus; DRESS, drug rash with eosinophilia and systemic symptoms; LC, Langerhans cells; OLP, oral lichen planus; PSO, psoriasis; T_RM, T-resident memory. This figure was created using images from Smart Servier (https://creativecommons.org/licenses/by/3.0/), WikiHow (https://creativecommons.org/licenses/by-nc-sa/3.0/) and Freepik.es (@brgf).