Crosstalk between ILC2s and Th2 cells varies among mouse models
Rama K. Gurram,
Danping Wei,
Qiao Yu,
Matthew J. Butcher,
Xi Chen,
Kairong Cui,
Gangqing Hu,
Mingzhu Zheng,
Xiaoliang Zhu,
Jangsuk Oh,
Bing Sun,
Joseph F. Urban, Jr.,
Keji Zhao,
Warren J. Leonard,
Jinfang Zhu
Affiliations
Rama K. Gurram
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA; Corresponding author
Danping Wei
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Qiao Yu
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Gerontology and Respirology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Matthew J. Butcher
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Xi Chen
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kairong Cui
Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Gangqing Hu
Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA
Mingzhu Zheng
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Xiaoliang Zhu
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Jangsuk Oh
Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
Bing Sun
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
Joseph F. Urban, Jr.
US Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA
Keji Zhao
Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Warren J. Leonard
Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
Jinfang Zhu
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Summary: Type 2 T helper (Th2) cells and group 2 innate lymphoid cells (ILC2s) provide protection against helminth infection and are involved in allergic responses. However, their relative importance and crosstalk during type 2 immune responses are still controversial. By generating and utilizing mouse strains that are deficient in either ILC2s or Th2 cells, we report that interleukin (IL)-33-mediated ILC2 activation promotes the Th2 cell response to papain; however, the Th2 cell response to ovalbumin (OVA)/alum immunization is thymic stromal lymphopoietin (TSLP) dependent but independent of ILC2s. During helminth infection, ILC2s and Th2 cells collaborate at different phases of the immune responses. Th2 cells, mainly through IL-4 production, induce the expression of IL-25, IL-33, and TSLP, among which IL-25 and IL-33 redundantly promote ILC2 expansion. Thus, while Th2 cell differentiation can occur independently of ILC2s, activation of ILC2s may promote Th2 responses, and Th2 cells can expand ILC2s by inducing type 2 alarmins.
