Figure legends
Figure 1. CLA+ memory T cells in the pathological mechanisms of AD. The memory phenotype of CLA+ T cells together with their selective migration to skin involve these cells in AD pathological mechanisms. By virtue of their de-homing capacity, circulating CLA+ T cells reflect cutaneous abnormalities present in AD lesions, includingS. aureus infection, abnormal Th2 immune response dominated by IL-13, and pruritogenic IL-31. Interestingly an early effect of dupilumab in AD treated patients is only reflected on circulating CLA+, but not CLA-, CD4+ CCR4+ T cells. AD, atopic dermatitis; APC, antigen presenting cell; CLA, cutaneous lymphocyte-associated antigen; HDM, house dust mite; MHC, major histocompatibility complex; S. aureus, Staphylococcus aureus ; SEB, staphylococcal enterotoxin B; TCR, T-cell receptor.
Figure 2. SEB, IL-13, and CCL17 mechanisms meet in CLA+ T cells in AD. SEB-specific TCR Vβ are preferentially expressed by CLA+ T cells that upon activation induce a predominant IL-13 response in the skin where abundant expression of IL-13Rα1 and IL-13Rα2 are found, and an IL-13 dominated transcriptional inflammatory signature is present. CLA+ T cells in AD present an epigenetic alteration for IL-13. SEB-induced IL-13 in CLA+ T cells relates to patients’ severity and plasma levels of IgE to S. aureus . Only IL-13, but not other SEB-induced cytokines, correlates with plasma levels of CCL17, one of the best biomarkers for AD, which is a ligand for CCR4 that attracts circulating CLA+CD4+ CCR4+ Th2 cells to skin. Additionally, IL-13 also correlates with CCL26 mRNA expression in lesional skin. AD, atopic dermatitis; APC, antigen presenting cell; CLA, cutaneous lymphocyte-associated antigen; EASI, eczema area and severity index; MHC-II, major histocompatibility complex class II; S. aureus, Staphylococcus aureus ; SEB, staphylococcal enterotoxin B; TCR, T-cell receptor.
Figure 3. HDM relates specific CLA+ T cell response with pruritus and IL-31. Circulating CLA+ T cells preferentially respond to HDM and share with infiltrating HDM-specific T cells same TCRB CDR3 regions. CD4+CLA+ T cells are the most abundant lymphocyte in AD lesions and major producers of IL-31. HDM-induced IL-31 by circulating CLA+ T cells correlated with patient´s pruritus, and plasma levels of periostin, in patients with HDM-specific IgE. On the other hand, plasma levels of the keratinocyte-derived CCL27, a ligand for CCR10 that is preferentially expressed by CLA+ T cells, correlates with HDM-induced IL-31. Interestingly, CCL27 in the stratum corneum is a biomarker of response to anti-IL31RA therapy in AD. AD, atopic dermatitis; APC, antigen presenting cell; CLA, cutaneous lymphocyte-associated antigen; HDM, house dust mite; MHC-II, major histocompatibility complex class II; TCR, T-cell receptor.