Group 2 Innate Lymphoid Cells Promote Development of Antigen-Specific Th2 Cells by Providing GM-CSF and Activating Dendritic Cells

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Presentation Time: 10:15 AM - 10:30 AM
Abstract ID: 4360 - B

Presenting Author:
Jared Brooksby , PhD Student at Mayo Clin. Grad. Sch. of Biomed. Sci.

Abstract:

Rationale

Lung group 2 innate lymphoid cells (ILC2s) rapidly respond to allergen exposure by producing various cytokines. The goal of this project was to investigate whether and how ILC2s contribute to the adaptive immunity in the lungs.

Methods ILC2-deficient (Il7r^Cre/+Rora^fl/fl) and control (Il7r^+/+Rora^fl/fl) mice were exposed intranasally (i.n.) to ovalbumin (OVA) antigen with fungus Alternaria extract as an adjuvant. Dendritic cells (DC) were analyzed 24 hours later. To evaluate antigen-specific adaptive immunity, mice were challenged i.n. with OVA alone. In vivo antibody neutralization, gene-deficient mice and adoptive transfer models were used to dissect the mechanisms involved.

Results ILC2-deficient mice previously exposed to OVA plus Alternaria and challenged i.n. with OVA antigen produced significantly less type 2 cytokines in the lungs as compared to control mice. Draining lymph node cells from ILC2-deficient mice failed to produce type 2 cytokines when stimulated with OVA in vitro. ILC2-deficient mice exposed to Alternaria  produced less GM-CSF than control mice. Administering GM-CSF-neutralizing antibody to wild-type mice before Alternaria exposure reduced DC activation and Th2 cell numbers in the lung. Adoptive transfer of wild-type, but not GM-CSF-deficient ILC2s, rescued DC activation and OVA-specific Th2 responses in ILC2-deficient mice.

Conclusion ILC2-derived GM-CSF is critical for DC activation and development of antigen-specific Th2 cells.