Role of macrophage migration inhibitory factor (MIF) in pollen-induced allergic conjunctivitis and pollen dermatitis in mice
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Updated: Apr 17, 2026

Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Yuka Nagata1, Yoko Yoshihisa1, Kenji Matsunaga1
1Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
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.
Insights
Macrophage migration inhibitory factor (MIF) drives allergic inflammation in pollen-induced conjunctivitis and dermatitis. Inhibiting MIF may offer a new treatment for these pollen allergies.
Area of Science:
- Immunology
- Allergology
- Dermatology
Background:
- Pollen is a common allergen causing allergic conjunctivitis and exacerbating atopic dermatitis (AD).
- Macrophage migration inhibitory factor (MIF) is a cytokine implicated in allergic inflammation and AD.
- Pollen-induced skin reactions around the eyes are termed pollen dermatitis.
Purpose of the Study:
- To investigate the role of MIF in pollen-induced allergic conjunctivitis and pollen dermatitis.
- To determine if MIF influences eosinophil infiltration and inflammatory gene expression in response to pollen exposure.
Main Methods:
- Utilized MIF knockout (KO), transgenic (Tg), and wild-type (WT) mice.
- Immunized mice with ragweed (RW) or Japanese cedar (JC) pollen and administered pollen via eye drops.
- Analyzed conjunctival and eyelid tissue for eosinophil infiltration and measured mRNA expression of key inflammatory mediators (eotaxin, IL-5, IL-13).
- Conducted in vitro studies using dermal fibroblasts to assess MIF's effect on eotaxin expression.
Main Results:
- MIF Tg mice showed significantly increased eosinophil infiltration in the conjunctiva and eyelids compared to WT and MIF KO mice after pollen sensitization.
- Elevated mRNA levels of eotaxin, IL-5, and IL-13 were observed in the eyelid skin of pollen-sensitized MIF Tg mice.
- In vitro, MIF combined with IL-4 or IL-13 strongly induced eotaxin expression in dermal fibroblasts, which was inhibited by CD74 siRNA.
Conclusions:
- MIF plays a critical role in promoting eosinophil accumulation in the conjunctiva and eyelid dermis following pollen exposure.
- Targeting MIF presents a potential therapeutic strategy for managing pollen-induced allergic conjunctivitis and pollen dermatitis.

