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Natural Helper Cells and TH2-Type Innate Immunity

Koyasu, Shigeo PhD

doi: 10.1097/ICO.0b013e318269cb1a

Abstract: Natural helper (NH) cells are a newly identified innate lymphocyte population, which respond to a combination of interleukin (IL)-2 and IL-25 or IL-33 to produce large amounts of TH2 cytokines, most notably, IL-5 and IL-13. We identified NH cells in lymphoid clusters in adipose tissues, which we termed fat-associated lymphoid clusters. IL-5 and IL-13 produced by activated NH cells induce eosinophilia and goblet cell hyperplasia, respectively, and play an important role in anti-helminth immunity and allergic diseases, such as asthma. In addition, NH cells produce TH2 cytokines constitutively in the absence of stimulation and support the self-renewal of B1 cells and IgA production by B cells. After our identification of NH cells, other groups have also reported novel TH2 cytokine–producing cells, such as nuocytes, and innate helper type 2 cells. There are similarities and differences between these newly identified cell populations and NH cells. Multipotent progenitor cell type 2 (MPPtype2) cells can differentiate to other myeloid cells, making this a distinct cell type from the others. MPPtype2 cells, nuocytes, and innate helper type 2 cells respond to IL-25 alone in vivo, whereas NH cells do not respond to IL-25 without IL-2, although they respond strongly to IL-33. Localization of NH cells in fat-associated lymphoid clusters is an intriguing difference compared with the other cell types, which are found in the lymph node and/or spleen. This article summarizes current information regarding the emerging field of TH2-type innate lymphocytes.

Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan and Laboratory for Immune Cell System, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.

Reprints: Shigeo Koyasu, Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan (e-mail:

Supported by a Grant-in-Aid for Scientific Research (No. 22229004) from the Japan Society for the Promotion of Science.

Dr Koyasu is a consultant for Medical and Biological Laboratories, Co, Ltd. The author has no other conflicts of interest, financial or otherwise, to declare.

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.