An Inhibitory Role for Sema4A in Antigen-Specific Allergic Asthma

作者：Morihana Tetsuo; Goya Sho; Mizui Masayuki; Yasui Teruhito; Prasad Durubaka V R; Kumanogoh Atsushi; Tamura Manabu; Shikina Takashi; Maeda Yohei; Iwamoto Yoriko; Inohara Hidenori; Kikutani Hitoshi^*

来源：Journal of Clinical Immunology, 2013, 33(1): 200-209.

DOI：10.1007/s10875-012-9798-5

• Sema4A
• T(H)1/T(H)2 regulation
• allergic asthma

Purpose The class IV semaphorin Sema4A is critical for efficient T(H)1 differentiation and Sema4a(-/-) mice exhibit impaired TH1 immune responses. However, the role of Sema4A in T(H)2 cell-mediated allergic diseases has not been fully studied. The aim of this study was to clarify the regulatory role possessed by Sema4A in mouse models of allergic diseases, particularly allergic asthma.
Methods Sema4a(-/-) mice on a BALB/c background were examined for the development of allergic diseases. To induce experimental asthma, mice were sensitized with ovalbumin (OVA) followed by intranasal challenges with OVA. After challenge, airway hyperreactivity (AHR) and airway inflammation were evaluated. The role of Sema4A in asthma was examined using Sema4a(-/-) mice and Sema4A-Fc fusion proteins. The direct effects of Sema4A-Fc on antigen-specific effector CD4(+) T cells were also examined.
Results A fraction of Sema4a(-/-) BALB/c mice spontaneously developed skin lesions that resembled atopic dermatitis (AD) in humans. Furthermore, AHR, airway inflammation, and TH2-type immune responses were enhanced in Sema4a(-/-) mice compared to wild type (WT) mice when immunized and challenged with OVA. In vivo systemic administration of Sema4A-Fc during the challenge period ameliorated AHR and lung inflammation and reduced the production of TH2-type cytokines inWT mice. The inhibitory effects of Sema4A on airway inflammation were also observed in mice deficient in Tim-2, a Sema4A receptor. Finally, we showed that Sema4A-Fc directly inhibited IL-4-producing OVA-specific CD4(+) T cells.
Conclusion These results demonstrate that Sema4A plays an inhibitory role in T(H)2-type allergic diseases, such as allergic asthma.

• 出版日期2013-1