Human oncostatin M deficiency underlies an inherited severe bone marrow failure syndrome.

Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM.

Decrease in CD38 TH2A cell frequencies following immunotherapy with house dust mite tablet correlates with humoral responses.

Background: In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi-food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM-AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells.

Methods: The frequencies of TH2A and CD38 TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM-allergic individuals included in a 1-year clinical trial assessing the efficacy of HDM tablets.

CCR10 ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma.

Background: We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10.

Method: Herein, CCR10 ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10 and CCR10 ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression.

Introduction: MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome.

Method: Using specific culture conditions, we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of T 1, T 2 or regulatory T cells, respectively).

Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy.

Background: Eligibility to immunotherapy is based on the determination of IgE reactivity to a specific allergen by means of skin prick or in vitro testing. Biomarkers predicting the likelihood of clinical improvement during immunotherapy would significantly improve patient selection.

Methods: Proteins were differentially assessed by using 2-dimensional differential gel electrophoresis and label-free mass spectrometry in pretreatment sera obtained from clinical responders and nonresponders within a cohort of 82 patients with grass pollen allergy receiving sublingual immunotherapy or placebo.

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

Background: We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections.

Objective: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.

Methods: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

Background: Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT).

Objectives: We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy.

Methods: Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively.

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

Objectives: Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero.

The BLNK adaptor protein has a nonredundant role in human B-cell differentiation.

Background: Expression of the pre-B-cell receptor (pre-BCR) by pre-BII cells constitutes a crucial checkpoint in B-cell differentiation. Mutations that affect the pre-B-cell receptor result in early B-cell differentiation blockades that lead to primary B-cell immunodeficiencies. BLNK adaptor protein has a key role in the pre-B-cell receptor signaling cascade, as illustrated by the abnormal B-cell development in the 4 patients with BLNK gene defects reported to date.

Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination.

Background: The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine.

Methods: Cells were investigated by karyotyping and gene expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC) compartment.

Identification of a new phenotype of tolerogenic human dendritic cells induced by fungal proteases from Aspergillus oryzae.

We characterized a new pathway to induce tolerogenic dendritic cells (DCs) following treatment of human monocyte-derived DCs with proteases from the fungus Aspergillus oryzae (ASP). ASP-treated DCs (ASP-DCs) exhibit a CD80(-)CD83(-)CD86(-)Ig-like transcript (ILT)2(-)ILT3(-)ILT4(+) phenotype, do not secrete cytokines or chemokines, and express tolerogenic markers such as glucocorticoid-induced leucine zipper, NO synthetase-2, retinaldehyde dehydrogenase-1 or retinaldehyde dehydrogenase-2. When cocultured with naive CD4(+) T cells, ASP-DCs induce an anergic state that can be reversed by IL-2.