Role of Siglec‐E in MC903‐Induced Atopic Dermatitis

ABSTRACT Atopic dermatitis (AD) is a common skin disease. Although AD pathogenesis has been widely researched, inhibitory mechanisms in AD are still unclear. Sialic acid‐binding immunoglobulin‐like lectins (Siglecs) are a family of receptors recognising sialic acids; most Siglecs work as inhibitory receptors. Among Siglecs, Siglec‐E is expressed on dendritic cells (DCs) and eosinophils, important immune cells in AD. Although Siglec‐E inhibits Type 1 inflammatory diseases, how it influences AD is unknown. Thus, we investigated the role of Siglec‐E in AD mouse model by using Siglec‐E knockout (KO) mice. We demonstrated that Siglec‐E attenuated AD‐like inflammation of mice caused by topical application of MC903 on ear skin (MC903‐induced AD). To reveal the role of Siglec‐E in MC903‐induced AD, we focused on Siglec‐E on DCs and eosinophils. We first showed that Sigle‐E was expressed on cutaneous DCs and migratory DCs of draining lymph nodes. Moreover, OX40L expression on cutaneous DCs was reduced in the presence of Siglec‐E. In vitro experiments using cultured spleen DCs (SpDCs), highly expressing Siglec‐E, revealed that IL‐33 was involved in the induction of Siglec‐E and confirmed that Siglec‐E inhibited OX40L expression on SpDCs induced by IL‐33. Moreover, CD4 + T cell–SpDC coculture revealed that Siglec‐E inhibited Th2 polarisation under IL‐33 stimulation. We finally revealed that Siglec‐E was expressed on eosinophils and reduced the eosinophils infiltration to the MC903‐treated ear skin with the suppression of CD49d, a necessary integrin for eosinophil migration to skin tissue [1], expression on eosinophils. These findings elucidated the inhibitory role of Siglec‐E in MC903‐induced AD.