2. Academic Validation
  3. Spatial distribution of IL4 controls iNKT cell-DC crosstalk in tumors

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

  • Cell Mol Immunol. 2020 May;17(5):496-506. doi: 10.1038/s41423-019-0243-z.
Lu Wang  # 1,  Zhilan Liu  # 1 2,  Lili Wang 1,  Qielan Wu 1,  Xiang Li 1,  Di Xie 1,  Huimin Zhang 1,  Yongdeng Zhang 2,  Lusheng Gu 2,  Yanhong Xue 2,  Ting Yue 3,  Gang Liu 4,  Wei Ji 2,  Haiming Wei 1,  Tao Xu 2,  Li Bai 5
Affiliations

Affiliations

  • 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.
  • 5 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. [email protected].
  • # Contributed equally.
PMID: 31160756 DOI: 10.1038/s41423-019-0243-z
Abstract

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 tumor-infiltrating iNKT cells, which impaired IL4 polarization and disturbed iNKT cell-DC crosstalk in tumors.

Keywords

Crosstalk; DC; IL4; Polarization; Spatial distribution; Tumor; iNKT.

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