Background
Atopic dermatitis (AD) is a heterogeneous disease, characterized by excess T helper (Th) 22 activation in Asian AD. Inducible T-cell costimulator (ICOS) is crucial for T-cell activation and differentiation. However, the role of ICOS in AD and its effect on Th22 cells remain unclear. Objectives: To gain a better understanding of the role of ICOS and ICOS ligand (ICOSL) in the pathogenesis of Asian AD and its underlying mechanisms.
Conclusions
Our findings demonstrate that ICOS/ICOSL expression and effects are linked to Th22 skewing and the pathogenesis of Han Chinese AD, which suggests ICOSL and ICOS as well as Th22 cells and IL-22 as new and promising therapeutic targets. What's already known about this topic? In Asian patients, atopic dermatitis (AD) is characterized by excess T helper (Th) 22 activation. Inducible T-cell costimulator (ICOS) is crucial for T-cell activation and differentiation. What does this study add? This study demonstrates that circulating Th22 cells, serum levels of interleukin (IL)-22 and IL-22+ cells are all markedly increased in lesional skin in Han Chinese patients with AD. In Han Chinese patients with AD, ICOS and ICOS ligand (ICOSL) drive Th22 skewing and increase filaggrin downregulation, and ICOS+ Th22 cells and ICOSL+ B cells are linked to disease activity. What is the translational message? ICOS+ Th22 cells and ICOSL+ B cells are potential clinical biomarkers of disease activity in Han Chinese patients with AD. ICOS- and ICOSL-targeted treatment approaches may benefit Han Chinese patients with AD.
Methods
We quantified ICOS and ICOSL expression in Han Chinese patients with AD and healthy controls (HC). Then, we assessed the proliferation and the production of the Th22 chemokines CCR4 and CCR10 by ICOSL-stimulated AD peripheral blood mononuclear cells (PBMCs) as well as their effects on keratinocyte filaggrin production. Finally, we explored the link between ICOS-expressing Th22 cells and disease activity and IgE levels in our patients with AD.
Results
Our patients with AD showed higher levels of ICOS-expressing Th22 cells as well as ICOSL-expressing CD19+ B cells and CD14+ monocytes compared with HC. ICOSL increased the proliferation and expression of CCR4 and CCR10, and of interleukin (IL)-22 in AD PBMCs. ICOSL treatment also significantly increased the downregulation of filaggrin expression by keratinocytes cocultured with PBMCs from patients with AD. Finally, blood levels of ICOS+ Th22 cells and ICOSL+ B cells in this AD cohort were correlated with disease activity as assessed by the SCORing Atopic Dermatitis index and with total IgE levels. In Han Chinese patients with AD, circulating Th22 cells, serum levels of IL-22 and IL-22+ cells in lesional skin were all markedly increased. Conclusions: Our findings demonstrate that ICOS/ICOSL expression and effects are linked to Th22 skewing and the pathogenesis of Han Chinese AD, which suggests ICOSL and ICOS as well as Th22 cells and IL-22 as new and promising therapeutic targets. What's already known about this topic? In Asian patients, atopic dermatitis (AD) is characterized by excess T helper (Th) 22 activation. Inducible T-cell costimulator (ICOS) is crucial for T-cell activation and differentiation. What does this study add? This study demonstrates that circulating Th22 cells, serum levels of interleukin (IL)-22 and IL-22+ cells are all markedly increased in lesional skin in Han Chinese patients with AD. In Han Chinese patients with AD, ICOS and ICOS ligand (ICOSL) drive Th22 skewing and increase filaggrin downregulation, and ICOS+ Th22 cells and ICOSL+ B cells are linked to disease activity. What is the translational message? ICOS+ Th22 cells and ICOSL+ B cells are potential clinical biomarkers of disease activity in Han Chinese patients with AD. ICOS- and ICOSL-targeted treatment approaches may benefit Han Chinese patients with AD.