IL-10-producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients.
BACKGROUND
Recently the immune regulatory role of T cell-derived IL-10 in allergic disease has been extensively studied. In contrast, there is mounting evidence that IL-10 might also have a role in the perpetuation of allergic inflammation and fibrotic remodeling. It has been reported that alternatively (IL-4) activated macrophages (aaMPhi) produce large quantities of IL-10 and lack IL-12 production.


OBJECTIVE
Bearing this in mind, we hypothesized whether functionally different properties of IL-10-producing monocytes could be identified.


METHODS
Intracellular cytokine expression of IL-10, IL-12, and IL-6 in peripheral blood CD14(+) monocytes was measured in 19 atopic patients and 18 healthy control subjects by means of flow cytometry. In addition, IL-10-secreting monocytes were sorted by means of flow cytometry. Capabilities of these cells regarding further differentiation, accessory cell capacity, and surface molecule expression were analyzed.


RESULTS
Our data show a dichotomous expression pattern of either IL-10 or IL-12p40/p70 in peripheral blood monocytes after LPS stimulation. Compared with healthy control subjects, the percentage of IL-10-producing monocytes was significantly increased in atopic patients. IL-10-secreting monocytes were isolated by using an IL-10 secretion assay, and functional analysis of these sorted cells revealed that IL-10-secreting monocytes preferentially differentiate into suppressor of cytokine signaling 3 expressing aaMPhi, which perpetuate T(H)2 immune response.


CONCLUSIONS
Our study shows the existence of an IL-10-producing monocyte subset, which is increased in atopic disease and which might facilitate allergic inflammation and fibrotic remodeling by differentiation into aaMPhi.


CONCLUSIONS
Controlling aaMPhi in T(H)2-driven inflammatory processes might be a novel target for intervention strategies.
Prasse
Antje
A
Department of Pneumology, University Hospital Freiburg, Freiburg, Germany. prasse@medizin.ukl.uni-freiburg.de <prasse@medizin.ukl.uni-freiburg.de>
Germann
Martin
M
Pechkovsky
Dmitri V
DV
Markert
Anna
A
Verres
Tibor
T
Stahl
Mirjam
M
Melchers
Inga
I
Luttmann
Werner
W
Müller-Quernheim
Joachim
J
Zissel
Gernot
G
D000328:Adult; D002454:Cell Differentiation; D018920:Coculture Techniques; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology
D008070:Lipopolysaccharides; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor