Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life

Tomer Granot; Takashi Senda; Dustin J Carpenter; Nobuhide Matsuoka; Joshua Weiner; Claire L Gordon; Michelle Miron; Brahma V Kumar; Adam Griesemer; Siu-Hong Ho; Harvey Lerner; Joseph J C Thome; Thomas Connors; Boris Reizis; Donna L Farber

doi:10.1016/j.immuni.2017.02.019

Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life

Immunity. 2017 Mar 21;46(3):504-515. doi: 10.1016/j.immuni.2017.02.019.

Authors

Affiliations

¹ Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
² Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
³ Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
⁴ Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
⁵ Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
⁶ LiveOnNY, New York, NY 10001, USA.
⁷ Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Division of Critical Care, Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.
⁸ Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA.
⁹ Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: df2396@cumc.columbia.edu.

Abstract

Maturation and migration to lymph nodes (LNs) constitutes a central paradigm in conventional dendritic cell (cDC) biology but remains poorly defined in humans. Using our organ donor tissue resource, we analyzed cDC subset distribution, maturation, and migration in mucosal tissues (lungs, intestines), associated lymph nodes (LNs), and other lymphoid sites from 78 individuals ranging from less than 1 year to 93 years of age. The distribution of cDC1 (CD141^hiCD13^hi) and cDC2 (Sirp-α⁺CD1c⁺) subsets was a function of tissue site and was conserved between donors. We identified cDC2 as the major mature (HLA-DR^hi) subset in LNs with the highest frequency in lung-draining LNs. Mature cDC2 in mucosal-draining LNs expressed tissue-specific markers derived from the paired mucosal site, reflecting their tissue-migratory origin. These distribution and maturation patterns were largely maintained throughout life, with site-specific variations. Our findings provide evidence for localized DC tissue surveillance and reveal a lifelong division of labor between DC subsets, with cDC2 functioning as guardians of the mucosa.

Keywords: dendritic cells; human immunology; mucosal immunity; tissue immunity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Dendritic Cells / cytology*
Female
Flow Cytometry
Fluorescent Antibody Technique
Humans
Infant
Male
Middle Aged
Young Adult

Abstract

Publication types

MeSH terms

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