IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients Antje Prasse, MD, Martin Germann,

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Presentation transcript:

IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients Antje Prasse, MD, Martin Germann, MD, Dmitri V. Pechkovsky, MD, Anna Markert, MD, Tibor Verres, MD, Mirjam Stahl, Inga Melchers, PhD, Werner Luttmann, PhD, Joachim Müller-Quernheim, MD, Gernot Zissel, PhD Journal of Allergy and Clinical Immunology Volume 119, Issue 2, Pages 464-471 (February 2007) DOI: 10.1016/j.jaci.2006.09.030 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 CD14+ monocytes from patients with atopic disease produce statistically significantly more IL-10 and less IL-12p40. A, Percentage of IL-10+ and IL-12p40+ monocytes after 12 hours of stimulation with LPS. Solid bars indicate control subjects, and open bars indicate patients with atopic disease. B, Production of IL-10 and IL-12p40 of monocytes stimulated with LPS for 48 hours (∗P < .05, ∗∗P < .005). C-F, Flow cytometric analysis of intracellular cytokine expression from a healthy volunteer (Fig 1, C) and a patient with atopic disease (Fig 1, D) is shown. The distribution of IL-10+ and IL-12+ production is merely dichotomous. In contrast, IL-6 is expressed in IL-10+, as well as in IL-12p40+, monocytes (Fig 1, E and F). Journal of Allergy and Clinical Immunology 2007 119, 464-471DOI: (10.1016/j.jaci.2006.09.030) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IL-10–secreting monocytes spontaneously express markers of macrophages and alternative activation. A and B disclose CD83 and CD1a expression of IL-10–secreting cells and non-IL-10–secreting monocytes (C) after 7 days of culture in the presence of IL-4 and GM-CSF. In contrast to non-IL-10–secreting monocytes, IL-10–secreting monocytes did not differentiate into dendritic cells (Fig 2, A, vs Fig 2, C). In Fig 2, B, neutralizing IL-10 antibodies were added, which partly restored the capacity of IL-10–secreting cells to differentiate into dendritic cells. D through F disclose histograms demonstrating the fluorescence intensity of CD16 (Fig 2, D), CD68 (Fig 2, E), or CD163 (Fig 2, F) of IL-10–secreting (gray line) and non-IL-10–secreting monocytes (black line). Control values are shown as gray areas. Journal of Allergy and Clinical Immunology 2007 119, 464-471DOI: (10.1016/j.jaci.2006.09.030) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 IL-10–secreting monocytes express IL-1ra, CCL18, and SOCS3. IL-10–secreting monocytes produce and express more IL-1ra (A) and CCL18 (B) than non-IL-10–secreting monocytes after 24 hours of cell culture. Left bars depict protein concentrations in conditioned culture medium. Right bars depict relative level of IL-1ra mRNA (n = 10, ∗P < .05, ∗∗P < .005). C depicts data from RT-PCR with SOCS3-specific oligonucleotide primers. Journal of Allergy and Clinical Immunology 2007 119, 464-471DOI: (10.1016/j.jaci.2006.09.030) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 IL-10–secreting monocytes exhibit decreased T-cell stimulatory capacity and favor TH2 immune responses. A, CD4+CD45RA+ T cells were cocultured with IL-10–secreting monocytes or non-IL-10–secreting monocytes in the presence of SEB. T-cell proliferation was measured on the basis of tritiated thymidine incorporation (∗∗P < .005). B, CD4+CD45RA+ T cells were cocultured with IL-10–secreting monocytes or non-IL-10–secreting monocytes, and cytokine secretion was analyzed. Data are presented as percentages of the calculated difference between IL-10–secreting monocytes versus non-IL-10–secreting monocytes (n = 10). There is a statistically significant reduction in IFN-γ production, as well as an increase in IL-13 production, by T cells stimulated with IL-10–secreting monocytes. Journal of Allergy and Clinical Immunology 2007 119, 464-471DOI: (10.1016/j.jaci.2006.09.030) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions