母乳を介した抗原の移行は免疫寛容を惹起してアレルギー喘息を予防する
Valerie Verhasselt1,2, Valerie Milcent1,2, Julie Cazareth2,3, Akira
Kanda4,5,6, Sebastien Fleury4,5,6, David Dombrowicz4,5,6, Nicolas
Glaichenhaus1,2 & Valerie Julia1,2
1 Institut National de la Sante et de la Recherche Medicale (INSERM), U924,
Universite de Nice-Sophia Antipolis
2 Universite de Nice-Sophia-Antipolis, 660 Route des Lucioles, Valbonne
F-06560, France.
3 Centre National de la Recherche Scientifique, UMR 6097, 660 Route des
Lucioles, Valbonne F-06560, France.
4 INSERM, U547, 1 Rue du Dr. Roux, Lille F-59000, France.
5 Institut Pasteur de Lille, 1 Rue du Dr. Roux, Lille F-59000, France.
6 Universite de Lille,1 Rue du Dr. Roux, Lille F-59000, France.
Correspondence to: Valerie Julia1,2 e-mail: vjulia@unice.fr
Correspondence to: Valerie Verhasselt1,2 e-mail: verhasselt@unice.fr
アレルギー喘息は、アレルゲンへの曝露に応じて起こる気道閉塞を特徴とする慢性疾患である。この疾患は、環境中に浮遊する抗原に対する2型ヘルパーT細胞の不適切な応答によって発症し、3億人が罹患している。罹患率はこの数十年間に大きく上昇したが、その最大の理由は環境要因の変化であると考えられる。乳児期の環境中の抗原への曝露は、喘息の発症にきわめて重要である。母乳育児とアレルギー疾患との関連に関する疫学研究の結果は一致したものではない。本論文では、授乳期のマウスの空気中アレルゲンへの曝露が、仔マウスの喘息発症に影響を及ぼすかどうかを検討した。空気中の抗原は母乳を介して母体から新生仔に効率よく移行し、免疫寛容の誘導には免疫グロブリンの移行を必要としないことがわかった。母乳育児によって誘導される免疫寛容は、授乳時のトランスフォーミング増殖因子（TGF）-βの存在に左右され、調節性CD4+Tリンパ球を介し、T細胞のTGF-βシグナル伝達に依存する。つまり、母乳を介して新生仔へ抗原が移行することにより経口免疫寛容誘導が惹起され、これがアレルギー性気道疾患に対する抗原特異的な保護作用につながる。本研究は、アレルギー疾患の発症を予防するための新たな戦略デザインへの道を開くと考えられる。
[原文]
Breast milk-mediated transfer of an antigen induces tolerance and protection
from allergic asthma
Valerie Verhasselt1,2, Valerie Milcent1,2, Julie Cazareth2,3, Akira
Kanda4,5,6, Sebastien Fleury4,5,6, David Dombrowicz4,5,6, Nicolas
Glaichenhaus1,2 & Valerie Julia1,2
1 Institut National de la Sante et de la Recherche Medicale (INSERM), U924,
Universite de Nice-Sophia Antipolis
2 Universite de Nice-Sophia-Antipolis, 660 Route des Lucioles, Valbonne
F-06560, France.
3 Centre National de la Recherche Scientifique, UMR 6097, 660 Route des
Lucioles, Valbonne F-06560, France.
4 INSERM, U547, 1 Rue du Dr. Roux, Lille F-59000, France.
5 Institut Pasteur de Lille, 1 Rue du Dr. Roux, Lille F-59000, France.
6 Universite de Lille,1 Rue du Dr. Roux, Lille F-59000, France.
Correspondence to: Valerie Julia1,2 e-mail: vjulia@unice.fr
Correspondence to: Valerie Verhasselt1,2 e-mail: verhasselt@unice.fr
Allergic asthma is a chronic disease characterized by airway obstruction in
response to allergen exposure. It results from an inappropriate T helper
type 2 response to environmental airborne antigens and affects 300 million
individuals1. Its prevalence has increased markedly in recent decades, most
probably as a result of changes in environmental factors2. Exposure to
environmental antigens during infancy is crucial to the development of
asthma3. Epidemiological studies on the relationship between breastfeeding
and allergic diseases have reached conflicting results4, 5, 6, 7, 8. Here,
we have investigated whether the exposure of lactating mice to an airborne
allergen affects asthma development in progeny. We found that airborne
antigens were efficiently transferred from the mother to the neonate through
milk and that tolerance induction did not require the transfer of
immunoglobulins. Breastfeeding-induced tolerance relied on the presence of
transforming growth factor (TGF)-β during lactation, was mediated by
regulatory CD4+ T lymphocytes and depended on TGF-β signaling in T cells.
In conclusion, breast milk-mediated transfer of an antigen to the neonate
resulted in oral tolerance induction leading to antigen-specific protection
from allergic airway disease. This study may pave the way for the design of
new strategies to prevent the development of allergic diseases.
自己免疫疾患のリスクに関するデータが集まりつつある
Lisa M Maier1 ＆ David A Hafler1
1. Lisa M. Maier and David A. Hafler are in the Division of Molecular
Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital,
Harvard Medical School, 77 Ave. Louis Pasteur NRB 641, Boston, MA 02115 and
at the Broad Institute of Harvard University and Massachusetts Institute of
Technology. e-mail:hafler@broad.mit.edu
全身性エリテマトーデス（SLE）の新しいリスク変異（特に、リンパ球のシグナル伝達経路での変異や免疫複合体の除去に関わるインテグリンでの変異）が発見された。この新たな手がかりを治療に結びけることが、医学者の課題である。
[原文]
The developing mosaic of autoimmune disease risk
Lisa M Maier1 ＆ David A Hafler1
1. Lisa M. Maier and David A. Hafler are in the Division of Molecular
Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital,
Harvard Medical School, 77 Ave. Louis Pasteur NRB 641, Boston, MA 02115 and
at the Broad Institute of Harvard University and Massachusetts Institute of
Technology. e-mail:hafler@broad.mit.edu
The discovery of new risk variants for systemic lupus erythematosis (SLE),
particularly around lymphocyte signaling pathways and integrins involved in
clearing complement, provides fresh insights into this common human
autoimmune disease. Understanding the role of the variants in disease
pathophysiology and translating these findings into new therapies present
major and urgent challenges to medical scientists.
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