CD11b+ lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation

• Published in: Nature communications Vol. 12; no. 1; pp. 5029 - 16
• Main Authors: Izumi, Gentaro, Nakano, Hideki, Nakano, Keiko, Whitehead, Gregory S., Grimm, Sara A., Fessler, Michael B., Karmaus, Peer W., Cook, Donald N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-08-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/21; 13/31; 38/39; 38/91; 631/250/1619/554/1898/1273; 631/250/1619/554/1898/1274; 631/250/2152/1566/1618; 631/250/2504/133/2505; 631/250/347; 64/60; Adoptive transfer; Adoptive Transfer - methods; Animals; Asthma - immunology; Asthma - metabolism; Asthma - pathology; Base Sequence; CCR7 protein; CD11b antigen; CD11b Antigen - immunology; CD11b Antigen - metabolism; CD200 antigen; CD4 antigen; Cdc2 protein; Cell differentiation; Cell Differentiation - physiology; Cells, Cultured; Cluster analysis; Coculture Techniques; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic structure; Differentiation (biology); Disease Models, Animal; Gene sequencing; Helper cells; House dust; Humanities and Social Sciences; IL-1β; Immune response; Inhalation; Interleukin 1; Lung - immunology; Lung - metabolism; Lung - pathology; Lungs; Ly-6 antigen; Lymphocytes; Lymphocytes T; Male; Maturation; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Phenotypes; Respiration; Science; Science (multidisciplinary); Single-Cell Analysis - methods; Subpopulations; Th17 Cells - cytology; Th17 Cells - immunology; Th2 Cells - cytology; Th2 Cells - immunology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25307-x

Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b
+
DCs (cDC2) are heterogeneous. Here, we report a population of cDCs that rapidly accumulates in lungs of mice following house dust extract inhalation. These cells are Ly-6C
+
, are developmentally and phenotypically similar to cDC2, and strongly promote Th17 differentiation ex vivo. Single cell RNA-sequencing (scRNA-Seq) of lung cDC2 indicates 5 distinct clusters. Pseudotime analysis of scRNA-Seq data and adoptive transfer experiments with purified cDC2 subpopulations suggest stepwise developmental progression of immature Ly-6C
+
Ly-6A/E
+
cDC2 to mature Ly-6C
–
CD301b
+
lung resident cDC2 lacking
Ccr7
expression, which then further mature into CD200
+
migratory cDC2 expressing
Ccr7
. Partially mature Ly-6C
+
Ly-6A/E
–
CD301b
–
cDC2, which express
Il1b
, promote Th17 differentiation. By contrast, CD200
+
mature cDC2 strongly induce Th2, but not Th17, differentiation. Thus, Th17 and Th2 differentiation are promoted by lung cDC2 at distinct stages of maturation.
Dendritic cells in the lung may be specialised to mediate specific types of immune function. Here the authors show that subpopulations of mouse CD11b
+
lung DC at different stages of maturation and phenotype can promote Th17 or Th2 CD4
+
T cell differentiation.