Allergic lung inflammation can be modulated by niacin and drives the development of glycolytic eosinophils

Eosinophils are key contributors to allergic pathology, however, increasingly eosinophils are described to have important roles in organ health and immunoregulation. The factors that define and regulate these diverse eosinophil functions remain poorly understood. Here we show the emergence of a lung-specific Siglec-F^hi inflammatory eosinophil subset that exhibits high glycolytic activity, mTOR activation and increased amino acid and glucose uptake. The emergence of glycolytic Siglec-F^hi inflammatory eosinophils was apparent in the lung in multiple models of type 2 inflammation and in response to influenza infection. Siglec-F^hi eosinophils present in the lung during allergic inflammation also expressed the niacin and butyrate receptor GPR109A and were niacin responsive. These findings reveal a unique metabolic phenotype of activated lung eosinophils and reveal niacin-GPR109A signaling as a regulator of allergic type 2 immune responses.