ORIGINAL ARTICLE: Impact of Female Sex Hormones on the Maturation and Function of Human Dendritic Cells

Segerer, Sabine; Müller, Nora; Brandt, Jens van den; Kapp, Michaela; Dietl, Johannes; Reichardt, Holger M.; Rieger, Lorenz; Kämmerer, Ulrike

doi:10.1111/j.1600-0897.2009.00726.x

Cited by 76 publications

(69 citation statements)

References 36 publications

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“…Similarly, expression of glucocorticoid-inducible TNFR (GITR) has been shown to occur in protective Treg cells (22). Induction of smDC has to date been experimentally achieved by DC stimulation under diminished inflammatory environments, such that are achieved by added vitamin D (23,24), , estrogen (25), MyD88 inhibitors (26), and IL-10 (27).…”

Section: Endritic Cells (Dc) Undergo Transition From Immature DCmentioning

confidence: 99%

α-1 Antitrypsin Promotes Semimature, IL-10–Producing and Readily Migrating Tolerogenic Dendritic Cells

Ozeri

Mizrahi

Shahaf

et al. 2012

The Journal of Immunology

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Tolerogenic IL-10–positive CCR7-positive dendritic cells (DC) promote T regulatory (Treg) cell differentiation upon CCR7-dependent migration to draining lymph nodes (DLN). Indeed, in human DC deficiencies, Treg levels are low. α-1 antitrypsin (AAT) has been shown to reduce inflammatory markers, promote a semimature LPS-induced DC phenotype, facilitate Treg expansion, and protect pancreatic islets from alloimmune and autoimmune responses in mice. However, the mechanism behind these activities of AAT is poorly understood. In this study, we examine interactions among DC, CD4+ T cells, and AAT in vitro and in vivo. IL-1β/IFN-γ–mediated DC maturation and effect on Treg development were examined using OT-II cells and human AAT (0.5 mg/ml). CCL19/21-dependent migration of isolated DC and resident islet DC was assessed, and CCR7 surface levels were examined. Migration toward DLN was evaluated by FITC skin painting, transgenic GFP skin tissue grafting, and footpad DC injection. AAT-treated stimulated DC displayed reduced MHC class II, CD40, CD86, and IL-6, but produced more IL-10 and maintained inducible CCR7. Upon exposure of CD4+ T cells to OVA-loaded AAT-treated DC, 2.7-fold more Foxp3+ Treg cells were obtained. AAT-treated cells displayed enhanced chemokine-dependent migration and low surface CD40. Under AAT treatment (60 mg/kg), DLN contained twice more fluorescence after FITC skin painting and twice more donor DC after footpad injection, whereas migrating DC expressed less CD40, MHC class II, and CD86. Intracellular DC IL-10 was 2-fold higher in the AAT group. Taken together, these results suggest that inducible functional CCR7 is maintained during AAT-mediated anti-inflammatory conditions. Further studies are required to elucidate the mechanism behind the favorable tolerogenic activities of AAT.

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Section: Endritic Cells (Dc) Undergo Transition From Immature DCmentioning

confidence: 99%

α-1 Antitrypsin Promotes Semimature, IL-10–Producing and Readily Migrating Tolerogenic Dendritic Cells

Ozeri

Mizrahi

Shahaf

et al. 2012

The Journal of Immunology

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show abstract

“…In humans, hCG was also able to significantly decrease T-cell stimulatory capacity of DC (Huck, Steck et al, 2005). In contrast, the phenotype of hCG-treated DC ressembeled that of matured DC expressing co-stimulatory molecules like CD 40, CD83 and CD 86 (Segerer, Muller et al, 2009). Thus, hCG seems to be able to induce a tolerogenic subtype of DC even though costimulatory molecules of the mature subtype were expressed.…”

Section: Hcgmentioning

confidence: 99%

“…Analysing the effects of progesterone on T lymphocytes, a direct and indirect inhibition of TH1 cell development was detected (Miyaura and Iwata, 2002a). DC cultured under the influence of progesterone changed their phenotype into an immunostimulatory maturated phenotype expressing co-stimulatory molecules (Ivanova, Kyurkchiev et al, 2005;Segerer, Muller et al, 2009). In contrast to effects seen for hCG and estradiol, the capacity of DC to stimulate T-cell proliferation was not significantly altered (Segerer, Muller et al, 2009).…”

Section: Progesteronementioning

confidence: 99%

“…DC cultured under the influence of progesterone changed their phenotype into an immunostimulatory maturated phenotype expressing co-stimulatory molecules (Ivanova, Kyurkchiev et al, 2005;Segerer, Muller et al, 2009). In contrast to effects seen for hCG and estradiol, the capacity of DC to stimulate T-cell proliferation was not significantly altered (Segerer, Muller et al, 2009). However, progesterone had profound effects on rat mDC by suppressing the production of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF) and interleukin 1beta (IL-1) as well as by inhibiting the DC-stimulated proliferation of T-cells (Butts, Shukair et al, 2007).…”

Section: Progesteronementioning

confidence: 99%

“…There is evidence that female sex hormones contribute to the modulation of decidual immune cells into tolerogenic subtypes (for review see: (Kyurkchiev, Ivanova-Todorova et al, 2010) and especially can impact on DC (Segerer, Muller et al, 2009). Thereby, the "micromilieu" determines if the captured antigens are presented in a tolerogenic or immune activating way resulting also in different phenotypes of DC.…”

Section: Introductionmentioning

confidence: 99%

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