Human CLA + memory T cell and cytokines in psoriasis

Psoriasis is a common inflammatory skin condition resulting from the interplay between epidermal keratinocytes and immunological cellular components. This sustained inflammation is essentially driven by pro-inflammatory cytokines with the IL-23/IL-17 axis playing a critical central role, as proved by the clinical efficacy of their blockade in patients. Among all the CD45R0+ memory T cell subsets, those with special tropism for cutaneous tissues are identified by the expression of the Cutaneous Lymphocyte-associated Antigen (CLA) carbohydrate on their surface, that is induced during T cell maturation particularly in the skin-draining lymph nodes. Because of their ability to recirculate between the skin and blood, circulating CLA+ memory T cells reflect the immune abnormalities found in different human cutaneous conditions, such as psoriasis. Based on this premise, studying the effect of different environmental microbial triggers and psoriatic lesional cytokines on CLA+ memory T cells, in the presence of autologous epidermal cells from patients, revealed important IL-17 cytokines responses that are likely to enhance the pro-inflammatory loop underlying the development of psoriatic lesions. The goal of this mini-review is to present latest data regarding cytokines implicated in plaque and guttate psoriasis immunopathogenesis from the prism of CLA+ memory T cells, that are specifically related to the cutaneous immune system

CLA+ T cell response to microbes in psoriasis

Streptococcus pyogenes throat infection is a clinically relevant trigger of both guttate and chronic plaque psoriasis, and it provides an ideal context in which to study the pathogenesis of these diseases using an antigen-dependent approach. Circulating cutaneous lymphocyte-associated antigen (CLA) positive (+) memory T cells are a subset of peripheral lymphocytes whose phenotype and function are related to immunological mechanisms in the skin. These cells are considered peripheral biomarkers of T-cell-mediated skin diseases. The coculture of autologous epidermal cells with CLA+ T cells from psoriasis patients activated by S. pyogenes allows the reproduction of the ex vivo initial molecular events that occur during psoriatic lesion formation. With cooperation of autologous epidermal cells, S. pyogenes selectively activates CLA+ T cells both in guttate and plaque psoriasis, inducing key mediators, including an IL-17 response. Here, we explore potential new mechanisms of psoriasis development including the influence of HLA-Cw6 on S. pyogenes CLA+ T cell activation in guttate psoriasis, the relevance of IL-9 on microbe induced IL-17 response in guttate and plaque psoriasis, and novel effector functions of Candida albicans. This review will summarize recent knowledge of psoriatic mechanisms elicited by microbes that have been studied through an innovative translational perspective based on CLA+ T cell-mediated cutaneous immune response

The translational relevance of human circulating memory cutaneous lymphocyte-associated antigen positive T cells in inflammatory skin disorders

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

Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement

BACKGROUND: The knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease, and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment. METHODS: Through the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and quantitative real-time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional (NLS-CSU) and lesional skin (LS-CSU) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs). RESULTS: From 39 genes differentially expressed in NLS-CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS-CSU with NLS-CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation, or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance is shown. CONCLUSION: The skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile

Memory T Cell subpopulations as early predictors of remission to vedolizumab in ulcerative colitis

Background: vedolizumab is a humanized monoclonal antibody targeting the α4β7 integrin used for the treatment of ulcerative colitis. Few biomarkers related to vedolizumab response have been identified. The aim of this work was to assess whether baseline circulating CD4+ and CD8+ memory T-lymphocyte subpopulations could help to identify patients with response to vedolizumab treatment in ulcerative colitis. Methods: prospective pilot study in 15 patients with active ulcerative colitis and previous failure to anti-TNFα starting vedolizumab treatment. Peripheral blood samples were obtained before the first dose of vedolizumab and at week 6 and 14 of treatment. Clinical remission was defined as a Mayo Clinic partial score of ≤2 points without any concomitant dose of steroids. Biochemical remission or endoscopic improvement was defined as fecal calprotectin <250 mcg/g or Mayo endoscopic subscore ≤1. Results: at week 14, nine patients achieved clinical remission and eight patients achieved biochemical remission or endoscopic improvement. Patients in clinical remission presented higher baseline CD8 α4β7 + memory T cells concentration when compared with patients with no remission. In addition, patients with biochemical remission or endoscopic improvement at week 14 presented higher baseline concentration of CD8 α4β7 + memory T cells. No differences were identified according to flare severity, extent of disease or type of anti-TNFα failure. There were no significant differences regarding changes in T cell subsets during vedolizumab induction. Conclusion: CD8+ α4β7 + memory T cells before starting vedolizumab therapy could be an early predictor of remission in ulcerative colitis patients and therefore help to select a subset of responders

Interplay between Humoral and CLA + T Cell Response against Candida albicans in Psoriasis

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA- cutaneous lymphocyte antigen (CLA)+/- T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA+ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA+ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients

SEB-induced IL-13 production in CLA+ memory T cells defines Th2 high and Th2 low responders in atopic dermatitis

Data de publicació electrónica: 30-06-202