“野生”マウスのアレルギー研究が衛生仮説を覆す(Allergy study on ‘wild’ mice challenges the hygiene hypothesis)

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2023-09-29 カロリンスカ研究所(KI)

“野生”マウスのアレルギー研究が衛生仮説を覆す(Allergy study on ‘wild’ mice challenges the hygiene hypothesis)
Photo: Getty Images

◆「ハイジーン仮説」と呼ばれる理論では、微生物との適度な接触がアレルギーの発症リスクを減少させる可能性が示唆されてきましたが、カロリンスカ研究所の研究者たちは、この仮説に疑問を投げかけます。彼らは、野生のマウスと通常の実験用マウスのアレルギー免疫反応を比較し、微生物による感染への高い曝露が、アレルギー免疫反応を増強する可能性があることを示しました。
◆炎症性抗体やT細胞の機能にはほとんど変化が見られず、善玉菌による抗炎症反応もアレルギー免疫反応を抑制することができないようでした。この研究結果は、アレルギーのメカニズムに関する理解を深め、臨床的なアプローチに影響を与える可能性があります。

<関連情報>

野生の微生物叢を持つ実験用マウスが強いアレルギー免疫反応を起こす Laboratory mice with a wild microbiota generate strong allergic immune responses

Junjie Ma,Egon Urgard,Solveig Runge,Cajsa H. Classon,Laura Mathä,Julian M. Stark,Liqin Cheng,Javiera A. Álvarez,Silvia von Zedtwitz,Austeja Baleviciute,Sergio Martinez Hoyer,Muzhen Li,Anne Marleen Gernand,Lisa Osbelt,Agata Anna Bielecka,Till R. Lesker,Huey-Jy Huang,Susanne Vrtala,Louis Boon,Rudi Beyaert,Mikael Adner,Itziar Martinez Gonzalez,Till Strowig,Juan Du,Susanne Nylén,Stephan P. Rosshart,and Jonathan M. Coquet
Science Immunology  Published:29 Sep 2023
DOI:https://doi.org/10.1126/sciimmunol.adf7702

Editor’s summary

The hygiene hypothesis proposes that early-life exposure to microbes protects against the development of allergies, a possible explanation for the alarming rise in allergic disorders in developed countries. However, a causal link between early-life infections and allergies is lacking. To uncover the impact of lifelong microbial exposure on the development of allergic inflammation, Ma and Urgard et al. compared experimental wildling mice, which have a representative breadth of naturally occurring pathogens, to specific pathogen–free mice. Surprisingly, when challenged with allergens, wildlings developed robust signs of pathological inflammation and allergic responses, with rapid expansion of TH2 cells in the lungs. The study identifies that increased microbial biodiversity in wildlings did not protect against allergic inflammation, in contrast to what would be predicted by the hygiene hypothesis. —Hannah Isles

Abstract

Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early-life microbial exposures impede the development of subsequent allergic disease. Recently developed “wildling” mice are genetically identical to standard laboratory specific pathogen–free (SPF) mice but are housed under seminatural conditions and have rich microbial exposures from birth. Thus, by comparing conventional SPF mice with wildlings, we can uncouple the impact of lifelong microbial exposures from genetic factors on the allergic immune response. We found that wildlings developed larger populations of antigen-experienced T cells than conventional SPF mice, which included interleukin-10–producing CD4 T cells specific for commensal Lactobacilli strains and allergy-promoting T helper 2 (TH2) cells. In models of airway exposure to house dust mite (HDM), recombinant interleukin-33, or Alternaria alternata, wildlings developed strong allergic inflammation, characterized by eosinophil recruitment, goblet cell metaplasia, and antigen-specific immunoglobulin G1 (IgG1) and IgE responses. Wildlings developed robust de novo TH2 cell responses to incoming allergens, whereas preexisting TH2 cells could also be recruited into the allergic immune response in a cytokine-driven and TCR-independent fashion. Thus, wildling mice, which experience diverse and lifelong microbial exposures, were not protected from developing pathological allergic immune responses. Instead, wildlings mounted robust allergic responses to incoming allergens, shedding new light on the hygiene hypothesis.

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