Severe
pruritus is a characteristic feature of
atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of
pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve
pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important
cytokine for regulating
pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with
IL-4, an important
cytokine in AD development. We found that IL-31RA expression was upregulated by
IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of
IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that
IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar
Glyteer, an
aryl hydrocarbon receptor (AHR)
ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether
Glyteer affects IL-31RA expression induced by
IL-4 stimulation.
Glyteer inhibited upregulation of IL-31RA expression induced by
IL-4 stimulation in a dose-dependent manner.
Glyteer also inhibited Ccl 17 and Ccl 22 production induced by
IL-4 and IL-31 stimulation. Taken together, these findings suggest that
Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs.