Abstract

Pollen is a clinically important airborne allergen and one of the major causes of allergic conjunctivitis. A subpopulation of patients with atopic dermatitis (AD) are also known to have exacerbated skin eruptions on the face, especially around the eyelids, after contact with pollen. This pollen-induced skin reaction is now known as pollen dermatitis. Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including AD. In this study, MIF knockout (KO), MIF transgenic (Tg) and WT littermate mice were immunized with ragweed (RW) pollen or Japanese cedar (JC) pollen and challenged via eye drops. We observed that the numbers of conjunctiva- and eyelid-infiltrating eosinophils were significantly increased in RW and JC pollen-sensitized MIF Tg compared with WT mice or MIF KO mice. The mRNA expression levels of eotaxin, interleukin (IL)-5 and IL-13 were increased in pollen-sensitized eyelid skin sites of MIF Tg mice. An in vitro analysis revealed that high eotaxin expression was induced in dermal fibroblasts by MIF combined with stimulation of IL-4 or IL-13. This eotaxin expression was inhibited by the treatment with CD74 siRNA in fibroblasts. These findings indicate that MIF can induce eosinophil accumulation in the conjunctiva and eyelid dermis exposed to pollen. Therefore, targeted inhibition of MIF might result as a new option to control pollen-induced allergic conjunctivitis and pollen dermatitis.

Highlights

  • Ragweed (RW) pollen is a clinically important airborne allergen in North America and is one of the major causes of allergic conjunctivitis

  • To examine the role of migration inhibitory factor (MIF) in the eosinophilic infiltration in the conjunctiva and eyelid, MIF KO, MIF Tg and WT mice were immunized with RW or Japanese cedar (JC) pollen and challenged via eye drops on the eye and the barrier-disrupted eyelid as described in the Materials and Methods section

  • The results showed that in both the conjunctiva and eyelid skin, only few eosinophils were present in non-sensitized control MIF KO, MIF Tg and WT mice, while eosinophilic infiltration of the conjunctival mucosa and the dermis was significantly increased following RW or JC sensitization

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Summary

Introduction

Ragweed (RW) pollen is a clinically important airborne allergen in North America and is one of the major causes of allergic conjunctivitis. MIF Induce Eosinophilia in Pollen Dermatitis environmental factors cause exacerbation of allergic dermatitis by penetrating barrier-disrupted skin. Pollen dermatitis is a recently identified disease characterized by itchy erythema of the skin during the Japanese cedar (JC) pollen season (February–April) [2]. It has been postulated that pollen dermatitis is triggered by the contact with cedar pollen Ag, i.e. airborne contact dermatitis, as skin symptoms characteristically appear on exposed areas, such as the face [3]. In some patients with AD, which is characterized by impaired skin barrier function, JC pollen can preferentially cause seasonal exacerbation of dermatitis in exposed areas [4]

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