Spatial distribution of IL4 controls iNKT cell-DC crosstalk in tumors  

作　　者：Lu Wang Zhilan Liu Lili Wang Qielan Wu Xiang Li Di Xie Huimin Zhang Yongdeng Zhang Lusheng Gu Yanhong Xue Ting Yue Gang Liu Wei Ji Haiming Wei Tao Xu Li Bai 

机构地区：[1]Division of Life Sciences and Medicine,Department of Oncology of The First Affiliated Hospital,The CAS Key Laboratory of Innate Immunity and Chronic Disease,University of Science and Technology of China,230027 Hefei,China [2]National Key Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,100101 Beijing,China [3]School of Life Sciences,University of Science and Technology of China,230027 Hefei,China [4]National Synchrotron Radiation Laboratory,University of Science and Technology of China,230027 Hefei,China

出　　处：《Cellular & Molecular Immunology》2020年第5期496-506,共11页中国免疫学杂志（英文版）

基　　金：This work was supported by National Key R&D Program of China 2017YFA0505300;the National Natural Science Foundation of China 91542203 and 81771671;the Strategic Priority Research Program of the Chinese Academy of Sciences XDA12030208;the Fundamental Research Funds for the Central Universities.

摘　　要：The spatiotemporal distribution of cytokines orchestrates immune responses in vivo,yet the underlying mechanisms remain to be explored.We showed here that the spatial distribution of interleukin-4(IL4)in invariant natural killer T(iNKT)cells regulated crosstalk between iNKT cells and dendritic cells(DCs)and controlled iNKT cell-mediated T-helper type 1(Th1)responses.The persistent polarization of IL4 induced by strong lipid antigens,that is,α-galactosylceramide(αGC),caused IL4 accumulation at the immunological synapse(IS),which promoted the activation of the IL4R-STAT6(signal transducer and activator of transcription 6)pathway and production of IL12 in DCs,which enhanced interferon-γ(IFNγ)production in iNKT cells.Conversely,the nonpolarized secretion of IL4 induced by Th2 lipid antigens with a short or unsaturated chain was incapable of enhancing this iNKT cell-DC crosstalk and thus shifted the immune response to a Th2-type response.The nonpolarized secretion of IL4 in response to Th2 lipid antigens was caused by the degradation of Cdc42 in iNKT cells.Moreover,reduced Cdc42 expression was observed in tumorinfiltrating iNKT cells,which impaired IL4 polarization and disturbed iNKT cell-DC crosstalk in tumors.

关 键 词：Spatial distribution Polarization IL4 iNKT DC CROSSTALK Tumor 

分 类 号：R73[医药卫生—肿瘤]