Lung natural helper cells are an important source of innate TH2 cytokines (158.2)

Abstract

Abstract Recently, novel innate TH2 cytokine producing lymphocytes termed nuocytes or natural helper cells have been found in the gut-associated mucosa tissues. Similar TH2 cytokine producing innate cells have also been detected in other organs, including the lung, but their functional significance is not well understood. We have identified TH2 cytokine producing innate lymphocytes, termed lung natural helper (NH) cells in B6 mouse lungs and elucidated their role in lung eosinophilia and asthma. Lung NH cells are Lineage-negative but express of Sca-1, c-Kit, CD127 and CD25. Lung NH cell gene expression microarrays indicate that they likely constitute a novel lymphoid lineage. When purified and stimulated in vitro, they produce large amounts of IL3, 4, 5, 13, and IL17A. They also rapidly produce IL5 and IL13 in lung explant cultures stimulated with IL25, an alarmin released by stressed lung epithelial cells. Lung NH cells are present in Rag-/- mice that lack T and B cells but absent in Rag-/-cγ-/- mice. Intranasal administration of protease allergen papain rapidly induces eosinophil infiltration and mucus hypersecretion, which are hallmark asthma symptoms, in the lung of B6 and Rag-/- mice but not in Rag-/-cγ-/- mice. Papain treatment of lung explants also induces IL13 production by lung NH cells. Thus, lung NH cells are unique lymphocytes of the innate immune system and an important source of T cell-independent TH2 cytokines. They likely play an important role in initiating asthma.