Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.
Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8(+) T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141(hi) DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c(+) and CD14(+) tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141(hi) DCs were closely related to blood CD141(+) DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Muzlifah
M
Haniffa
Amanda
A
Shin
Venetia
V
Bigley
Naomi
N
McGovern
Pearline
P
Teo
Peter
P
See
Pavandip Singh
PS
Wasan
Xiao-Nong
XN
Wang
Frano
F
Malinarich
Benoit
B
Malleret
Anis
A
Larbi
Pearlie
P
Tan
Helen
H
Zhao
Michael
M
Poidinger
Sarah
S
Pagan
Sharon
S
Cookson
Rachel
R
Dickinson
Ian
I
Dimmick
Ruth F
RF
Jarrett
Laurent
L
Renia
John
J
Tam
Colin
C
Song
John
J
Connolly
Jerry K Y
JK
Chan
Adam
A
Gehring
Antonio
A
Bertoletti
Matthew
M
Collin
Florent
F
Ginhoux
D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism*; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D012867:Skin / Q000276:immunology; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000941:Antigens; D015703:Antigens, CD; D054357:Chemokine CXCL10; D039001:Integrin alpha Chains; D014409:Tumor Necrosis Factor-alpha; C091367:alpha E integrins