Toward homeostasis: regulatory dendritic cells from the bone marrow of mice with inflammation of the airways and peritoneal cavity

Naomi M Scott; Royce L X Ng; Deborah H Strickland; Jacqueline L Bisley; Scott A Bazely; Shelley Gorman; Mary Norval; Prue H Hart

doi:10.1016/j.ajpath.2012.04.007

Toward homeostasis: regulatory dendritic cells from the bone marrow of mice with inflammation of the airways and peritoneal cavity

Am J Pathol. 2012 Aug;181(2):535-47. doi: 10.1016/j.ajpath.2012.04.007. Epub 2012 Jun 5.

Authors

Naomi M Scott¹, Royce L X Ng, Deborah H Strickland, Jacqueline L Bisley, Scott A Bazely, Shelley Gorman, Mary Norval, Prue H Hart

Affiliation

¹ Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia.

PMID: 22677422
DOI: 10.1016/j.ajpath.2012.04.007

Abstract

Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow. In this study, DCs (CD11c(+) cells) differentiated from the bone marrow of mice with inflammation of the airways, or the peritoneal cavity had poor priming ability resulting in reduced, long-lived responses to that antigen in vivo. This indicates enhancement of regulatory mechanisms of immune responses through a peripheral tissue-bone marrow axis. If CD11c(+) cells, expanded from the bone marrow of mice with tissue inflammation were antigen pre-loaded and injected into mice already sensitized to that antigen, then subsequent contact hypersensitivity responses were significantly reduced. The effects of inflammation were imprinted in vivo and were independent of in vitro culture conditions for DC differentiation. The effect of tissue inflammation on the bone marrow DC precursors was not detected in mice treated subcutaneously with slow-release indomethacin pellets, suggesting a role for prostanoids, including prostaglandin E(2), in differentiation of regulatory CD11c(+) cells from bone marrow. Our study represents an important homeostatic process with potential for therapeutic use in the future.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alum Compounds
Animals
B7-2 Antigen / metabolism
Bone Marrow Cells / drug effects
Bone Marrow Cells / immunology*
Bone Marrow Cells / pathology*
CD11c Antigen / metabolism
Cell Differentiation / drug effects
Cell Movement / immunology
Cross-Priming / immunology
Dendritic Cells / drug effects
Dendritic Cells / enzymology
Dendritic Cells / immunology*
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Haptens / immunology
Homeostasis / drug effects
Homeostasis / immunology*
Hypersensitivity / complications
Hypersensitivity / immunology
Hypersensitivity / pathology
Immunization
Indomethacin / pharmacology
Inflammation / complications
Inflammation / immunology
Inflammation / pathology*
Interleukin-4 / pharmacology
Lung / drug effects
Lung / immunology
Lung / pathology*
Lung Diseases / complications
Lung Diseases / immunology
Lung Diseases / pathology
Lymph Nodes / drug effects
Lymph Nodes / pathology
Membrane Proteins / pharmacology
Mice
Mice, Inbred BALB C
Myelopoiesis / drug effects
Ovalbumin / immunology
Peritoneal Cavity / pathology*

Substances

Alum Compounds
B7-2 Antigen
CD11c Antigen
Haptens
Membrane Proteins
flt3 ligand protein
Interleukin-4
aluminum sulfate
Granulocyte-Macrophage Colony-Stimulating Factor
Ovalbumin
Indomethacin