Circulating CLA⁺T cells in atopic dermatitis and their possible role as peripheral biomarkers

Abstract

Cutaneous lymphocyte-associated antigen (CLA + ) T cells are specialized for skin homing and represent the main T-cell population in atopic dermatitis (AD) lesions. CLA + is expressed on the surface of circulating CD45RO + memory T cells and most skin-infiltrating T cells. Mechanistic studies and thus treatment advancements are limited by the need of large number of skin biopsies. Circulating CLA + T cells may be a reliable surrogate marker of the inflammatory events occurring in the skin, and thus, the evaluation of CLA + T cells in the blood may eliminate the need for skin biopsies. Preliminary work in AD has established that disease-associated T-cell abnormalities can be approached by either a study of skin lesions or activated CLA + T-cell subsets in peripheral blood. Future studies in adults and children, across different skin disorders, correlating blood and skin phenotypes and determining skin-homing T-cell functional properties are needed to establish whether CLA + memory subsets can be used as biomarkers and a substitute for skin biopsies. This review summarizes the latest advancements reached on circulating CLA + in AD and the great potential they harbor in understanding AD mechanisms.

Efficacy and safety of ustekinumab treatment in adults with moderate‐to‐severe atopic dermatitis

“…This study also presents several limitations: (i) a clear limitation is that the study has been designed a few years ago without knowledge of pharmacokinetics or drug durability in AD patients, and therefore, psoriasis dosing intervals 31 were chosen; (ii) we also failed to appreciate the magnitude of systemic inflammation in patients with moderate-to-severe AD, which is significantly larger than in psoriasis, as evidenced by the observation that T cells, particularly in the peripheral blood, show much stronger signs of activation in AD than in psoriasis as assessed by ICOS expression, a marker of T-cell activation. 32,33 This hyperactivation in patients with moderateto-severe AD might lead to accelerated clearance of target-bound ustekinumab and/or the need for either higher or more frequent dosing of ustekinumab in this disease. This is also supported by a recent report of a patient with severe, recalcitrant AD that has been treated effectively with much shorter intervals of ustekinumab given every 8 weeks 16 ; (iii) the treatment effect might be partially masked due to use of background topical GCS.…”

Microbe-Dependent Induction of IL-9 by CLA+ T Cells in Psoriasis and Relationship with IL-17A

“…Given the biomarker capacity of peripheral CLA þ T cells, they may provide evidence of relevant disease-associated inflammatory mediators (Czarnowicki et al, 2017;Ferran et al, 2013a). In our model, IL-9, together with IL-17A and IFN-g, was preferentially produced by psoriatic memory CLA þ T cells upon activation with SE and in the presence of autologous lesional epidermal cells.…”

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood

“…Cutaneous lymphocyte antigen (CLA þ ) memory T cells are peripheral biomarkers in inflammatory skin disorders (Czarnowicki et al, 2017b). We evaluated activated CD4 þ / CD8 þ T cells and their differentiation to IFN-g-, IL-13-, IL-22-, IL-17A-, and IL-9-producing T cells within skin homing/CLA þ and systemic/CLA e compartments in blood of patients with ichthyosis, compared to patients with AD and psoriasis and healthy controls.…”