Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life.
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 (CD141hiCD13hi) 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-DRhi) 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.
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.
Tomer
T
Granot
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.
Takashi
T
Senda
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.
Dustin J
DJ
Carpenter
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.
Nobuhide
N
Matsuoka
Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Joshua
J
Weiner
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.
Claire L
CL
Gordon
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.
Michelle
M
Miron
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Brahma V
BV
Kumar
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.
Adam
A
Griesemer
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.
Siu-Hong
SH
Ho
LiveOnNY, New York, NY 10001, USA.
Harvey
H
Lerner
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.
Joseph J C
JJC
Thome
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.
Thomas
T
Connors
Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA.
Boris
B
Reizis
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.
Donna L
DL
Farber
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
dendritic cells; human immunology; mucosal immunity; tissue immunity