Cross-Comparison of Inflammatory Skin Disease Transcriptomics Identifies PTEN as a Pathogenic Disease Classifier in Cutaneous Lupus Erythematosus.

Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases.

Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance.

Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections.

Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance.

Transcriptomics Analysis Indicates Trifarotene Reverses Acne-Related Gene Expression Changes.

Trifarotene is a topical retinoid selective for retinoic acid receptor gamma that was recently approved for treatment of acne vulgaris. We performed a gene expression analysis to identify the molecular and cellular impact of trifarotene treatment on acne papules. In this open-label prospective study, subjects with moderate inflammatory acne of the back were treated with trifarotene 0.

Optimised generation of iPSC-derived macrophages and dendritic cells that are functionally and transcriptionally similar to their primary counterparts.

Induced pluripotent stem cells (iPSC) offer the possibility to generate diverse disease-relevant cell types, from any genetic background with the use of cellular reprogramming and directed differentiation. This provides a powerful platform for disease modeling, drug screening and cell therapeutics. The critical question is how the differentiated iPSC-derived cells translate to their primary counterparts.

Determination of T Follicular Helper Cell Fate by Dendritic Cells.

T follicular helper (Tfh) cells are a specialized subset of CD4 T cells that collaborate with B cells to promote and regulate humoral responses. Unlike other CD4 effector lineages, Tfh cells require interactions with both dendritic cells (DCs) and B cells to complete their differentiation. While numerous studies have assessed the potential of different DC subsets to support Tfh priming, the conclusions of these studies depend heavily on the model and method of immunization used.

Migratory CD11b conventional dendritic cells induce T follicular helper cell-dependent antibody responses.

T follicular helper (Tfh) cells are a subset of CD4 T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen.

Differential Intrasplenic Migration of Dendritic Cell Subsets Tailors Adaptive Immunity.

Evidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in vitro. Therefore, we tested whether the organization of DC and T cell subsets in the spleen dictated this preference.

Bridging channel dendritic cells induce immunity to transfused red blood cells.

Red blood cell (RBC) transfusion is a life-saving therapeutic tool. However, a major complication in transfusion recipients is the generation of antibodies against non-ABO alloantigens on donor RBCs, potentially resulting in hemolysis and renal failure. Long-lived antibody responses typically require CD4(+) T cell help and, in murine transfusion models, alloimmunization requires a spleen.

Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice results in defective dendritic cell migration.

Dendritic cells (DCs) are the primary leukocytes responsible for priming T cells. To find and activate naïve T cells, DCs must migrate to lymph nodes, yet the cellular programs responsible for this key step remain unclear. DC migration to lymph nodes and the subsequent T-cell response are disrupted in a mouse we recently described lacking the NOD-like receptor NLRP10 (NLR family, pyrin domain containing 10); however, the mechanism by which this pattern recognition receptor governs DC migration remained unknown.

Beyond pattern recognition: NOD-like receptors in dendritic cells.

Innate instruction of adaptive immunity was proposed more than 20 years ago as a mechanism by which long-lived lymphocyte responses are targeted to appropriate antigens. At the time Charles Janeway proposed this theory, most of the innate immune receptors were unknown, and the pivotal role of the dendritic cell in instructing T cell priming was debated. There is now overwhelming evidence that the innate and adaptive branches of the immune system must interact to generate immunity.

Absence of Foxp3+ regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation.

Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear.

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia.

Dendritic cells derived from HOXB4-immortalized hematopoietic bone marrow cells.

Dendritic cells (DCs) are essential for the generation and modulation of cell-mediated adaptive immunity against infections. DC-based vaccination involves transplantation of ex vivo-generated DCs loaded with antigen in vitro, but remains limited by the number of autologous or allogeneic cells. While in vitro expansion and differentiation of hematopoietic stem cells (HSCs) into DCs seems to be the most viable alternative to overcome this problem, the complexity of HSC expansion in vitro has posed significant limitations for clinical application.

Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.

Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection.

The synthetic TLR2 agonist BPPcysMPEG leads to efficient cross-priming against co-administered and linked antigens.

The property of DC to generate effective CTL responses is influenced by TLR signaling. TLR ligands contain molecular signatures associated with pathogens, have an impact on the antigen processing and presentation by DC, and are being exploited as potential adjuvants. We hypothesized that the TLR2/6 heterodimer agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide-2, is a potent adjuvant for cross-priming against cellular antigens.