Murine polymicrobial sepsis is associated with a sustained reduction of dendritic cell (DC) numbers in lymphoid organs and with a dysfunction of DC that is considered to mediate the chronic susceptibility of post-septic mice to secondary infections. We investigated whether polymicrobial sepsis triggered an altered de novo formation and/or differentiation of DC in the bone marrow. BrdU labeling experiments indicated that polymicrobial sepsis did not affect the formation of splenic DC. DC that differentiated from bone marrow (bone marrow-derived DC [BMDC]) of post-septic mice released enhanced levels of IL-10 but did not show an altered phenotype in comparison with BMDC from sham mice. Adoptive transfer experiments of BMDC into naive mice revealed that BMDC from post-septic mice impaired Th1 priming but not Th cell expansion and suppressed the innate immune defense mechanisms against Pseudomonas bacteria in the lung. Accordingly, BMDC from post-septic mice inhibited the release of IFN-γ from NK cells that are critical for the protection against Pseudomonas. Additionally, sepsis was associated with a loss of resident DC in the bone marrow. Depletion of resident DC from bone marrow of sham mice led to the differentiation of BMDC that were impaired in Th1 priming similar to BMDC from post-septic mice. Thus, in response to polymicrobial sepsis, DC precursor cells in the bone marrow developed into regulatory DC that impaired Th1 priming and NK cell activity and mediated immunosuppression. The absence of resident DC in the bone marrow after sepsis might have contributed to the modulation of DC differentiation.

Atopic dermatitis (AD) is a chronic inflammatory disease controlled by the innate and adaptive immune system. To elucidate the impact of innate immune signaling in AD, we analyzed MyD88-deficient mice in a murine model of AD-like dermatitis by epicutaneous sensitization with ovalbumin (OVA). Global MyD88 deficiency led to reduced epidermal thickening and diminished accumulation of macrophages within the inflamed skin. In addition, we observed impaired emigration of Langerhans cells (LCs) out of the epidermis of MyD88-deficient mice. These findings indicate that MyD88 deficiency affects various skin-resident cell types in the AD model. Moreover, production of IFN-g, IL-17, and CCL17 was reduced in skin draining lymph node cells and OVA-specific immunoglobulin levels were lower in MyD88-deficient mice. We further investigated the role of MyD88 in keratinocytes, as keratinocytes contribute to AD pathology. Exclusive expression of MyD88 in epidermal keratinocytes partially restored LC emigration after AD induction and expression of CCL17 in skin draining lymph nodes (LNs), but did not promote epidermal thickening nor production of IL-17. Altogether, these data demonstrate that MyD88 signaling in keratinocytes is able to restore LC migration in an otherwise MyD88-deficient background, and significantly contributes to the development of AD-like dermatitis.Keywords: Allergology r Dermatitis r Innate immunity r Langerhans cells r MyD88 signaling r Skin inflammation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAtopic dermatitis (AD) is a chronic, inflammatory skin disease [1,2] characterized by pruritic, scaly, and erythematous skin lesions and is caused by genetic, environmental, and immunologic factors Correspondence: Dr. Heike Weighardt e-mail: Heike.weighardt@uni-bonn.de [3]. Activation of the immune system during AD results in a mixed Th1 and Th2 response, but also Th22 and Th17 subsets contribute to the immune response [4]. In the majority of AD patients the disease is associated with the development of allergen-specific IgE titers, however also a non-IgE-associated form exists [2]. * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 982Sonja Didovic et al. Eur. J. Immunol. 2016. 46: 981-992 The development of AD involves barrier defects caused by mutations in structural genes such as filaggrin or disturbed protease activity in the epidermis [5,6] and a dysregulation of the immune system of the skin [6,7]. Impaired barrier function is characterized by enhanced transepidermal water loss (TEWL), which may enhance entry of pathogens, allergens, or toxins and thereby facilitate activation of the skin immune system [6,7]. The skin dendritic cell (DC) network comprises epidermal Langerhans cells (LCs) and different subsets of dermal DCs (dDCs) [8,9]. Upon antigen acquisition both LCs and dDCs get activated and migrate to the draining lymph nodes (LNs) to induce an immune re...

the Republic of) and 2 Hisol, Namwon, Korea (the Republic of) Development of new efficient cosmeceuticals is one of hot competitive fields in skin research due to its potential as new therapeutic modalities besides their original concept of supportive care. As candidate materials for new cosmeceuticals, herb extracts are regarded to be ideal candidates due to their known safety in human bodies. This study was performed to determine the antioxidant activity of essential oils and hydrosols, which extracted from naturallyoccurring herbs in NHEKs. To select candidate herb products with a potent antioxidant activity, cells were treated with the following products: Lavernder; Lemongrass; Rosemary; Peppermint; and Chamomile oil and hydrosol, respectively. To determine the scavenging activity of products, cells were treated with 50 mJ/cm 2 of UVB, and then immediately harvested for assaying total ROS levels by using the DCFDA-cellular reactive oxygen species detection assay kit. To determine antioxidant expression levels, NHEKs were treated with oil and hydros products for 24 hrs, and RT-PCR and Western blot analysis were performed. In DCFDA assay by FACS analysis and confocal microscopic experiments, all of tested herb products have a ROS-scavenging activities to inhibit UVB-induced ROS production. In RT-PCR and Western blot analysis, all of tested products induced the up-regulation of expression levels of Cu-zn SOD, MnSOD, GPx II, Prx I and a set of Nrf-2-dependent phase 2 enzymes, such as HO-1, NQO-1, GSTA4, GSTpi, in a dose-dependent manner. Nrf-2 transcriptional factor was up-regulated as it was translocated to the nucleus, indicating the Nrf-2-dependent modulation of phase 2 enzymes. In summary, our tested herb extracts of oil products and hydrosol are revealed to have a potent antioxidant activity by modulating ROS-scavenging enzymatic antioxidants and Nrf 2-dependent phase 2 enzymes in NHEKs. From our study, we propose a set of candidate herb extracts, which can be used for important sources for new cosmeceuticals in future.