Determine neuro-immune changes during aging using a model of allergic disease.
Immunology
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
The Aim of the research Project was to determine age related changes in the perception of allergens by sensory neurons, as well as to characterize age related changes in the neuropeptide release response and downstream activation of immune cells associated with allergic sensitization. By observing a decreased allergic sensitization with age in the human population, we hypothesized that age related changes in the response of sensory neurons to allergens might be a reason for a decreased type-2 immune response with age. Indeed, we found that perception of allergen induced itch is decreased during aging while the perception of itch trough nonallergic pruritogens and the perception of pain remains unchanged. Respectively, the release of Substance P after immunization with the protease allergen papain is reduced in aged sensory neurons in vivo and in vitro, pointing to a decreased sensory neuron response towards allergens in aged mice. Interestingly, the activation and migration of CD301b+ Th2 skewing DCs from the side of immunization within the skin to the draining lymph node was unchanged. Moreover, the cytokine expression of CD4+ T-helper cells in the draining lymph node (LN) 5 days after immunization did not show any change in Th2 associated IL4+ and IL4+ IL13+ CD4 cells but a significant increase in IFNg (Th1 cytokine) producing CD4+ cells. This data reveals a shift in the affinity towards the induction of a type 1 immune response rather than a type 2 immune response in aged mice, although the capacity to produce Th2 skewing cytokines remains unchanged. In conclusion, the results of the proposed research project point towards a fundamental change in the response and function of sensory neurons to certain allergens with age while the ability of antigen presenting cells to get activated and migrate into the draining LN as well as the ability of CD4+ T-helper cells to produce type 2 cytokines like IL4 and IL13 stays unchanged with age.
Publications
- Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens. Immunity. November 17, 2020
Perner C, Flayer CH, Zhu X, Aderhold PA, Dewan ZNA, Voisin T, Camire RB, Chow OA, Chiu IM, Sokol CL
(See online at https://doi.org/10.1016/j.immuni.2020.10.001) - A decision tree model for neuroimmune guidance of allergic immunity. Immunology and Cell Biology. June 2021
Flayer CH, Perner C, Sokol CL
(See online at https://doi.org/10.1111/imcb.12486) - Protocol for dissection and culture of murine dorsal root ganglia neurons to study neuropeptide release. STAR Protoc. 2021 Mar 19; 2(1):100333
Perner C, Sokol CL
(See online at https://doi.org/10.1016/j.xpro.2021.100333) - The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch. Proc Natl Acad Sci U S A. 2021 Mar 30; 118(13)
Voisin T, Perner C, Messou MA, Shiers S, Ualiyeva S, Kanaoka Y, Price TJ, Sokol CL, Bankova LG, Austen KF, Chiu IM, Chiu IM
(See online at https://doi.org/10.1073/pnas.2022087118) - Endoplasmic Reticulum Stress and Its Role in Homeostasis and Immunity of Central and Peripheral Neurons. Front Immunol. 2022;13:859703
Perner C, Kruger E
(See online at https://doi.org/10.3389/fimmu.2022.859703)
