Determine neuro-immune changes during aging using a model of allergic disease.

• Applicant: Dr. Caroline Perner
• Subject Area: Dermatology ; Immunology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 440737046

Interactions between the nervous system and the immune system have an outstanding importance in multiple types of diseases. The group of Dr. Caroline L. Sokol at Massachusetts General Hospital has found that itch sensing (pruritogenic) TRPV1+ neurons are activated by allergens and that activation of pruritogenic TRPV1+ neurons leads to an itch response as well as to release of the neuropeptide Substance P that activates allergic-skewing CD301b+ dendritic cells (DCs). These CD301b+ dermal DCs migrate into the draining lymph node (dLN) within 24h where they induce Th2 differentiation. Thus, activation of the TRPV1+ itch response is directly linked to the activation of the Type-2, or allergic immune response. Using this knowledge about the connections between pruritus and allergic immune sensitization, we propose to study a central paradox in Type-2 immunity: why does allergic sensitization decrease with age while at the same time the incidence of chronic pruritus increases with age? To address this, we plan to use behavioral analysis as well as ex vivo and in vitro stimulation assays to study sensory neuron activation in response to itch and pain inducing stimuli in young and old mice. Furthermore, we will use models of in vivo and in vitro DC migration to study the age related changes of DC migration with the ultimate aim to identify fundamental mechanisms underlying decreased allergen sensitization in the elderly. A better understanding of the effects of age-related neurodegenerative processes in the peripheral nervous system and how they affect the initiation of immune responses will uncover the fundamental processes controlling neuro-immune initiation of allergic disease and may reveal novel targets for the treatment of allergic diseases and chronic pruritus.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Caroline Lauren Sokol