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.