TY - JOUR
T1 - The Spectrum and Regulatory Landscape of Intestinal Innate Lymphoid Cells Are Shaped by the Microbiome
AU - Gury-BenAri, Meital
AU - Thaiss, Christoph Alexander
AU - Serafini, Nicolas
AU - Winter, Deborah R
AU - Giladi, Amir
AU - Lara Astiaso, Astiaso, David
AU - Levy, Maayan
AU - Salame, Tomer Meir
AU - Weiner, Assaf
AU - David, Eyal
AU - Shapiro, Hagit
AU - Dori-Bachash, Mally
AU - Pevsner-Fischer, Meirav
AU - Lorenzo Vivas, Vivas, Erika
AU - Keren-Shaul, Hadas
AU - Paul, Franziska
AU - Harmelin, Alon
AU - Eberl, Gerard
AU - Itzkovitz, Shalev
AU - Tanay, Amos
AU - Di Santo, Santo, James P
AU - Elinav, Eran
AU - Amit, Ido
N1 - We thank the members of I.A.’s and E.E.’s labs for fruitful discussions, Carmit Bar-Nathan for GF mouse care taking, Elena Kartvelishvily for help with electron microscopy, Melanie Flach for technical advice, and Maayan Wigelmann for art work. C.A.T. received a Boehringer Ingelheim Fonds PhD Fellowship. E.E. is supported by Y. and R. Ungar; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Gurwin Family Fund for Scientific Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Crown Endowment Fund for Immunological Research; the estate of J. Gitlitz; the estate of L. Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; the Adelis Foundation; J.L. and V. Schwartz; A. and G. Markovitz; A. and C. Adelson; the French National Center for Scientific Research (CNRS); D.L. Schwarz; the V.R. Schwartz Research Fellow Chair; L. Steinberg; J.N. Halpern; A. Edelheit, and by grants funded by the European Research Council; a Marie Curie Integration grant; the German-Israeli Foundation for Scientific Research and Development; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; the Helmholtz Foundation; and the European Foundation for the Study of Diabetes. E.E. is the incumbent of the Rina Gudinski Career Development Chair and a senior fellow of the Canadian Institute For Advanced Research (CIFAR). I.A. is supported by the European Research Council (309788), the I-CORE for chromatin and RNA regulation, and personal grants from the Israel Science foundation (782/11) and the BLUEPRINT FP7 consortium, the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, a Minerva Stiftung research grant, the National Human Genome Research Institute Center for Excellence in Genome Science (1P50HG006193), the Israeli Ministry of Science, Technology and Space, the David and Fela Shapell Family Foundation, and the Abramson Family Center for Young Scientists. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair.
PY - 2016/8/25
Y1 - 2016/8/25
N2 - Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remains elusive. Here, we combine genome-wide RNA-seq, ChIP-seq, and ATAC-seq tocompare the transcriptional and epigenetic identityof small intestinal ILCs, identifying thousands ofdistinct gene profiles and regulatory elements. Single-cell RNA-seq and flow and mass cytometry analyses reveal compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.
AB - Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remains elusive. Here, we combine genome-wide RNA-seq, ChIP-seq, and ATAC-seq tocompare the transcriptional and epigenetic identityof small intestinal ILCs, identifying thousands ofdistinct gene profiles and regulatory elements. Single-cell RNA-seq and flow and mass cytometry analyses reveal compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.
UR - http://www.scopus.com/inward/record.url?scp=84983780960&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2016.07.043
DO - 10.1016/j.cell.2016.07.043
M3 - مقالة
SN - 0092-8674
VL - 166
SP - 1231-1246.e13
JO - Cell
JF - Cell
IS - 5
ER -