P2RX7 regulates lung CD4+ T cell responses to allergens in a sensitization route-dependent way

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B858
Abstract ID: 5146

Presenting Author:
Bruna de Gois Macedo , Research Technologist at Mayo Clin., Arizona

Abstract:

CD4+ T cell responses to allergens vary depending on the route of sensitization, but the mechanisms behind these differences are not clear. CD4+ T cells are not only controlled by TCR:MHC and co-stimulation, but also by damage signals from the microenvironment. Extracellular ATP (eATP) is a danger signal released by inflamed tissues and sensed by immune cells via P2RX7. The role of P2RX7 in CD4+ T cell responses to allergen is unclear, with past reports suggesting opposite effects of P2RX7 knockout (KO). Here, we tracked the role of P2RX7 on allergen lung CD4+ T cells in response to different routes of sensitization. Comparing House Dust Mite (HDM) intranasal sensitization to subcutaneous sensitization with Ovalbumin (OVA)/Alum, we found increased lung inflammation, granulocyte infiltration, and lung CD4+CD69+GATA3+ T cells in response to subcutaneous OVA/Alum, compared to HDM. P2RX7-KO led to decreased lung CD4+ T cell responses (and reduced inflammation) in mice exposed to subcutaneous OVA/Alum, but not HDM. Importantly, we found the same discrepancies between routes of sensitization, as well as in the role of P2RX7, when comparing subcutaneous versus intranasal OVA/Papain sensitization – that is, systems with equal antigen and adjuvant. Our results provide additional evidence that the route of sensitization determines the type and magnitude of lung CD4+ T cell responses to allergen, and P2RX7 is important to dictate the intensity of subcutaneous allergen-induced responses.