Background Dendritic cells localize throughout the body, where they can sense

Background Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0098-y) contains supplementary material, which is available to authorized users. Background Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that can induce and direct host immune responses towards immunity or tolerance [1]. DCs disseminate throughout the body, sensing invading pathogens in various tissues, including the skin [2-4] and mucosa [5-7]. Therefore, defining the biology of tissue-resident DCs is fundamental for the understanding of tissue-specific immune microenvironments and for the rational design Alogliptin Benzoate of vaccines that can mount protective immunity in these tissues. Sexually transmitted microbial pathogens, including viruses and bacteria [8,9], are a major public health burden worldwide. The human vaginal mucosa is the main entry site of these pathogens and therefore has long been attractive as a potential site for mounting protective mucosal immunity. However, the vaginal mucosa, a site constantly exposed to foreign antigens, is also thought to be a unique tolerogenic microenvironment that tightly regulates unwanted immune responses [10-12]. Nonetheless, the immunology of the human vagina remains poorly understood. We recently reported the presence of four major subsets of APCs in the human vaginal mucosa, including Langerhans cells (LCs) in the epithelium, and CD14- DCs, CD14+ DCs and macrophages (M?s) in the lamina propria (LP) [5,6]. These mucosal APC subsets display common and unique functions in directing T-cell responses [5,6], as do subsets of DCs isolated from human skin [2-4]. Importantly, DCs can display functional specialization and plasticity in response to external and internal stimuli [13,14], which can determine the outcome of host immune responses. Recent evidence further indicates Rabbit polyclonal to ATF2 that these characteristics of DCs can be influenced by tissue-specific physical and biological factors [15,16]. One can thus hypothesize that the same DC subsets localized in different tissues could display distinct functions in response to the same antigens. These differences may also influence the type of immunity established in different human anatomical sites. As such, vaccines delivered to skin DCs can elicit systemic immunity but are not sufficient to mount mucosal immunity [6,10,17]. Systems biology approaches Alogliptin Benzoate provide snapshots of genetic, transcriptional and protein networks, enabling the phenotypic and functional analysis of the immune system [18-20]. In Alogliptin Benzoate this study, we investigated the phenotype and function of human vaginal DC subsets by microarray transcriptional profiling and compared them with those of DCs from human skin and blood. This study provides fundamental information for the immunology of human vaginal mucosa versus skin, which can eventually guide the rational design of efficacious vaccines against sexually transmitted pathogens. Methods Samples Vaginal and skin tissues were obtained from female patients who underwent pelvic or cosmetic surgeries under protocols approved by the Institutional Review Board of Baylor Research Institute (Dallas, TX, USA). Informed consent was waived by the institutional review board (IRB 008-227) for tissue samples. This study conforms to the Helsinki Declaration. Patients were not infected with HIV, hepatitis C virus or tuberculosis and did not display inflammation in the tissues. Written informed consent was obtained from healthy female volunteers to use their blood in this study, and the protocol was approved by the IRB (IRB 012-200) of Baylor Research Institute. Vaginal and skin antigen-presenting cell isolation Tissue biopsies were cut into 1?cm2 pieces Alogliptin Benzoate and incubated in phosphate-buffered saline containing bacterial protease dispase type 2 (Roche Applied Science, Indianapolis, IN, USA) and antibiotic/antimycotic solution (Invitrogen, Carlsbad, CA, USA) overnight at 4C. Epithelium and LP were then separated. The LP was cut into smaller pieces (1 to 5?mm2). Epithelial sheets and LP pieces were incubated at 37C in RPMI 1640 (Invitrogen) supplemented with HEPES buffer (Invitrogen), antibiotic/antimycotic (Invitrogen), L-glutamine, nonessential amino.

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