Efficient generation of human immune system rats using human CD34 cells.

Human immune system (HIS) mice generated using human CD34 hematopoietic stem cells serve as a pivotal model for the in vivo evaluation of immunotherapies for humans. Yet, HIS mice possess certain limitations. Rats, due to their size and comprehensive immune system, hold promise for translational experiments.

Changes in social behavior with MAPK2 and KCTD13/CUL3 pathways alterations in two new outbred rat models for the 16p11.2 syndromes with autism spectrum disorders.

Copy number variations (CNVs) of the human 16p11.2 locus are associated with several developmental/neurocognitive syndromes. Particularly, deletion and duplication of this genetic interval are found in patients with autism spectrum disorders, intellectual disability and other psychiatric traits.

CD4 and CD8 regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model.

Background: Regulatory T cells (Treg) in diverse species include CD4 and CD8 T cells. In all species, CD8 Treg have been only partially characterized and there is no rat model in which CD4 and CD8 FOXP3 Treg are genetically tagged.

Results: We generated a Foxp3-EGFP rat transgenic line in which FOXP3 gene was expressed and controlled EGFP.

On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes.

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing.

Disease modifying therapies and disease activity during pregnancy and postpartum in a contemporary cohort of relapsing Multiple Sclerosis patients.

Background: In Multiple Sclerosis (MS) women, therapeutic management for pregnancy planning and during pregnancy still represents a challenge regarding timing of disease-modifying therapies (DMT) stop, risk of disease reactivation and potential fetal toxicity. The objective of this study was to describe disease activity during pregnancy and postpartum depending on treatment status before conception in women with MS.

Methods: 339 MS patients who have achieved a pregnancy between 2007 and 2017 were included.

TNB-738, a biparatopic antibody, boosts intracellular NAD+ by inhibiting CD38 ecto-enzyme activity.

Cluster of differentiation 38 (CD38) is an ecto-enzyme expressed primarily on immune cells that metabolize nicotinamide adenine dinucleotide (NAD+) to adenosine diphosphate ribose or cyclic ADP-ribose and nicotinamide. Other substrates of CD38 include nicotinamide adenine dinucleotide phosphate and nicotinamide mononucleotide, a critical NAD+ precursor in the salvage pathway. NAD+ is an important coenzyme involved in several metabolic pathways and is a required cofactor for the function of sirtuins (SIRTs) and poly (adenosine diphosphate-ribose) polymerases.

COPP-MS: COrticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients.

Background: No specific treatment has demonstrated its effectiveness to prevent post-partum relapses for multiple sclerosis (MS) women.

Objective: To assess the effectiveness of preventive high-dose corticosteroids in the post-partum period by comparing two strategies: (1) no preventive treatment and (2) standardized preventive treatment.

Methods: We selected five French Multiple Sclerosis centers using the same post-partum strategy for their patients-either high-dose steroids (treating centers TC) or no treatment (non-treating centers NTC).

A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway.

BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis, and transcription. The largest isoform, BAG1L, controls the activity of the androgen receptor (AR) and is upregulated in prostate cancer.

Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes.

Background: While Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN.

Methods: We included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort.

Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection.

Background: Growing evidence suggest that type 2 immune effectors play a role in solid organ transplantation. The aim of this study was to evaluate the impact of blood count eosinophils (BCEo) on immunological outcomes in kidney transplant recipients with stable graft function after 3 months post-transplant.

Method: We performed cause-specific Cox model considering BCEo, the use of calcineurin inhibitors and systemic corticoids as time-dependent explicative variables on a prospective cohort of 1013 kidney transplant patients who experienced kidney allograft rejection and/or the appearance of de novo donor specific antibodies after excluding common causes of increased BCEo.

Type 2 immunity-driven diseases: Towards a multidisciplinary approach.

Asthma, atopic dermatitis and chronic rhinoconjunctivitis are highly heterogeneous. However, epidemiologic associations exist between phenotypic groups of patients. Atopic march is one such association but is not the only common point.

Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis.

Background And Aims: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray.

Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies.

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn's disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β).

Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment .

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits.

Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial.

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC).

Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens.

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens.

IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases.

Although IL-34 and CSF-1 share actions as key mediators of monocytes/macrophages survival and differentiation, they also display differences that should be identified to better define their respective roles in health and diseases. IL-34 displays low sequence homology with CSF-1 but has a similar general structure and they both bind to a common receptor CSF-1R, although binding and subsequent intracellular signaling shows differences. CSF-1R expression has been until now mainly described at a steady state in monocytes/macrophages and myeloid dendritic cells, as well as in some cancers.

Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients.

Background And Objectives: Keratinocyte cancers, which primarily comprise squamous cell carcinomas and basal cell carcinomas, represent a major concern and potential risk for kidney transplant recipients. Hydrochlorothiazide, a diuretic widely used to treat hypertension, has been implicated in skin photosensitivity reaction. Recent studies conducted in the general population have found that hydrochlorothiazide use is associated with a higher risk of keratinocyte cancer, especially squamous cell carcinomas.

Overexpression of endothelial β -adrenergic receptor induces diastolic dysfunction in rats.

Aims: Diastolic dysfunction is common in cardiovascular diseases, particularly in the case of heart failure with preserved ejection fraction. The challenge is to develop adequate animal models to envision human therapies in the future. It has been hypothesized that this diastolic dysfunction is linked to alterations in the nitric oxide ( NO) pathway.

Corrigendum: FB5P-seq: FACS-Based 5-Prime End Single-Cell RNA-seq for Integrative Analysis of Transcriptome and Antigen Receptor Repertoire in B and T Cells.

[This corrects the article DOI: 10.3389/fimmu.2020.