4.8 Article

Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity

Journal

IMMUNITY
Volume 50, Issue 2, Pages 505-+

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2019.01.012

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Funding

  1. National Institutes of Health [NIH P01AI06697, AI074878, AI095466, AI095608, AI102942, F32 DK109630, F32 AI134018-01]
  2. NIAID Mucosal Immunology Studies Team (MIST)
  3. Burroughs Wellcome Fund
  4. Crohn's & Colitis Foundation of America
  5. Weill Cornell Medicine Pre-Career Award
  6. Novo Nordic Foundation [14052]
  7. Leona M. and Harry B. Helmsley Charitable Trust [2014PG-IBD016]
  8. Cure for IBD
  9. NIAID [K22 AI116729]
  10. Rosanne H. Silberman Foundation

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Innate lymphoid cells (ILC) play critical roles in regulating immunity, inflammation, and tissue homeostasis in mice. However, limited access to non-diseased human tissues has hindered efforts to profile anatomically-distinct ILCs in humans. Through flow cytometric and transcriptional analyses of lymphoid, mucosal, and metabolic tissues from previously healthy human organ donors, here we have provided a map of human ILC heterogeneity across multiple anatomical sites. In contrast to mice, human ILCs are less strictly compartmentalized and tissue localization selectively impacts ILC distribution in a sub-set-dependent manner. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population heterogeneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distribution, subset heterogeneity, and functional potential of ILCs in non-diseased human tissues.

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