Repository logo
 

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Schlitzer, Andreas 
Teo, Pearline 
Zelante, Teresa 
Atarashi, Koji 

Abstract

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

Description

Keywords

Animals, Aspergillus fumigatus, CD11b Antigen, CD24 Antigen, Cell Differentiation, Dendritic Cells, Humans, Interferon Regulatory Factors, Interleukin-17, Interleukin-23, Intestinal Mucosa, Macrophages, Mice, Receptors, IgG, Respiratory Mucosa, Th17 Cells, fms-Like Tyrosine Kinase 3

Journal Title

Immunity

Conference Name

Journal ISSN

1074-7613
1097-4180

Volume Title

38

Publisher

Elsevier BV