Lipopolysaccharide impacts murine CD103 DC differentiation, altering the lung DC population balance.

TitleLipopolysaccharide impacts murine CD103 DC differentiation, altering the lung DC population balance.
Publication TypeJournal Article
Year of Publication2019
AuteursBrassard, J, Maheux, C, Langlois, A, Bernatchez, E, Marsolais, D, Flamand, N, Blanchet, M-R
JournalEur J Immunol
Volume49
Issue4
Pagination638-652
Date Published2019 Apr
ISSN1521-4141
Abstract

Conventional DCs are a heterogeneous population that bridge the innate and adaptive immune systems. The lung DC population comprises CD103 XCR1 DC1s and CD11b DC2s; their various combined functions cover the whole spectrum of immune responses needed to maintain homeostasis. Here, we report that in vivo exposure to LPS leads to profound alterations in the proportions of CD103 XCR1 DCs in the lung. Using ex vivo LPS and TNF stimulations of murine lung and spleen-isolated DCs, we show that this is partly due to a direct downregulation of the GM-CSF-induced DC CD103 expression. Furthermore, we demonstrate that LPS-induced systemic inflammation alters the transcriptional signature of DC precursors toward a lower capacity to differentiate into XCR1 DCs. Also, we report that TNF prevents the capacity of pre-DCs to express CD103 upon maturation. Overall, our results indicate that exposure to LPS directly impacts the capacity of pre-DCs to differentiate into XCR1 DCs, in addition to lowering their capacity to express CD103. This leads to decreased proportions of CD103 XCR1 DCs in the lung, favoring CD11b DCs, which likely plays a role in the break in homeostasis following LPS exposure, and in determining the nature of the immune response to LPS.

DOI10.1002/eji.201847910
Alternate JournalEur. J. Immunol.
PubMed ID30707446
Grant List / / JD Begin/CRIUCPQ Foundation /
/ / Canadian Institutes of Health Research /