The influence of viral infection on therapeutic immune tolerance in allergic airways disease.

过敏性呼吸道疾病，如哮喘，在儿童中呈上升趋势。不同的环境过敏原（如花粉）可引发过敏。在易感儿童中，吸入过敏原可能引起过敏反应和呼吸问题，有时需要住院治疗。用小的过敏原片段进行治疗，称为肽基免疫疗法（PIT），可以使过敏患者产生耐受性，即对过敏原无反应，没有过敏反应的风险。对过敏原的耐受性是如何形成的尚不完全清楚。儿童通常遭受病毒感染，如普通感冒，有时会发展过敏性呼吸道疾病。发生这种情况的原因尚不清楚，但人们认为病毒感染干扰了维持耐受性的免疫细胞。因此，如果PIT与病毒感染同时发生，它可能是无效的，甚至是有害的。使用小鼠模型，我将研究免疫细胞如何促进PIT后耐受性的发展。然后，我将确定病毒感染对这些细胞的影响以及PIT诱导耐受性的能力。如果PIT要安全地用于治疗过敏儿童，了解这些相互作用是至关重要的。此外，我的研究将进一步加深我们对病毒诱发过敏的机制的理解。

Allergic airways disease such as asthma is rising in children. Allergy can be triggered by different environmental allergens (e.g. pollen). In susceptible children, inhaling allergens may cause allergic reactions with breathing problems, sometimes requiring hospital treatment. Treatment with small allergen fragments, called peptide-based immunotherapy (PIT), can render allergic patients tolerant, i.e. unresponsive to their allergen, without the risk of allergic reactions. How tolerance to allergen develops is not fully understood. Children commonly suffer from viral infections such as the common cold and can sometimes develop allergic airways disease thereafter. Why this happens is unclear, but it is thought that viral infections interfere with the immune cells that maintain tolerance. Thus, there is concern that PIT may be ineffective or even detrimental if it coincides with a viral infection. Using a mouse model, I will study how immune cells contribute to the development of tolerance following PIT. I will then determine the effects of viral infection both on these cells and on the ability of PIT to induce tolerance. Understanding these interactions is vital if PIT is to be used safely in treating children with allergy. In addition, my studies will further our understanding of the mechanisms underlying virus induced allergy.