Increased frequencies of IL‐31‐producing T cells are found in chronic atopic dermatitis skin

Abstract

Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL-31, IFN-c, IL-13, IL-17 and IL-22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL-31-producing T cells compared to autologous blood and donor skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22, but rarely IFN-c or IL-17. A substantial part of the IL-31-producing T cells did not co-produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2 ⁄ Tc2 and Th22 ⁄ Tc22 cells, while frequencies of Th1 ⁄ Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL-31 at protein level in skin-infiltrating T cells. We show here that T cells in chronic AD skin produce IL-31 and that AD lesions contain increased levels of these IL-31-producing T cells. This suggests that a substantial part of previously reported increased IL-31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD.

NFAT1 and JunB Cooperatively Regulate IL-31 Gene Expression in CD4+ T Cells in Health and Disease

“…The human IL-31 promoter (827 bp) contains conserved binding sites for several transcription factors such as NFAT, STAT6, AP-1 and NF-kB. Among the factors, NFAT2 and STAT6 played a major role in activation of its promoter activity (32). We also tested whether NFAT2 and STAT6 could activate mouse IL-31 promoter as well.…”

Biomarkers for atopic dermatitis

“…[95][96][97][98][99] Nemolizumab is a humanized anti-human IL-31 receptor A antibody that was recently tested in phase I and II trials. Interestingly, we found an almost black and white difference in IL-31 expression levels in serum.…”

The atopic skin‐like microenvironment modulates the T‐cell‐polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry

“…In AD, mDCs are actively involved in the initiation and maintenance of skin inflammation, and the enhanced migration of these cells coincides with the eruption of skin lesions (3). The tissue microenvironment tightly controls mDC activation, which initiates the differentiation and lineage commitment of several skin-infiltrating Th subpopulations (Th2, Th1 and Th22 cells in the chronic phase of AD) (4)(5)(6). Characteristic features of the skin microenvironment include skin colonisation with superantigenproducing Staphylococcus aureus, which correlates with the severity of the disease, and the presence of thymic stromal lymphopoietin (TSLP), which is strongly overproduced by keratinocytes in lesional and non-lesional skin due to skin barrier dysfunction (7)(8)(9)(10)(11).…”