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.
Highlights
The existence of a cutaneous immune system in humans was postulated almost 50 years ago [1] and recently reformulated [2]
The goal of this review is to present latest results in the field of cutaneous lymphocyte-associated antigen (CLA)+ T cells in T cell-mediated inflammatory skin diseases and their translational relevance for human immunodermatology
CLA is more than a mere cell surface carbohydrate [3], preferentially expressed on CD45RO+ T cells, which binds to endothelial E-selectin and mediates cell adhesion and transendothelial migration together with other molecules such as lymphocyte function-associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), and C–C chemokine receptor type 10 (CCR10) [4]
Summary
The existence of a cutaneous immune system in humans was postulated almost 50 years ago [1] and recently reformulated [2]. IL-15 and IL-23, both present in psoriatic lesions, have been shown to synergize with CLA+ T cells and autologous epidermal cells to produce IL17A and IL-17F in PSO This phenomenon occurs without the use of any exogenous stimulus, in a major histocompatibility complex (MHC)-dependent way, and independently of resident T cells [18], but it does not take place using CLA− T cells or cells from healthy controls. Shin et al [21] developed psoriatic human 3D skin constructs (pHSCs) by incorporating T cells, over the classical approach based on the use of patientderived keratinocytes or fibroblasts treated with PSO-related cytokines As lymphocyte source, they tested in vitro polarized Th1/Th17 cells and CCR6+ CLA+ T cells from the patients with PSO, both of which showed psoriatic phenotype on epidermal cells along with disease-associated cytokine profile. A reduction on the number of CLA+ Th17/Tc17 and Th22/Tc22 cells was observed after 6 weeks of phototherapy and balneotherapy, which positively correlated with the reduction on PSO area and severity index (PASI) score [24]
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