Biology subjects

Braudeau, C.

Publications and source records attributed to Braudeau, C..

5 recordsLinked to original sources

bioRxiv2026

A JAK-STAT-activated myeloid hub at ulceration sites underlies resistance to anti-TNF therapy in Crohn's disease

Despite major advances in immunotherapies, durable disease control in immune-mediated inflammatory diseases (IMIDs) is frequently limited by resistance driven by maladaptive immune programs, resulting in progressive tissue damage. Myeloid cells are central effectors across IMIDs, including inflammatory bowel disease (IBD), yet how discrete myeloid states govern disease progression and therapeutic response remains incompletely defined. Here, using integrative single-cell transcriptomic and molecular analyses of inflamed human ileum in Crohns disease (CD), we identify combinatorial transcriptional programs that revealed previously unrecognized axes of monocyte-macrophage (mo-mac) heterogeneity. These myeloid states and programs were conserved and validated across multiple independent cohorts. We delineate a pathogenic mo-mac subset, interferon-associated inflammatory monocytes (IFIM), shaped by convergent NF-{kappa}B and IFN{gamma} signaling and enriched in advanced disease. Baseline abundance of IFIM programs predicted resistance to anti-TNF therapy and severe postoperative recurrence, with IFIM-derived ligands sustaining epithelial injury. IFIM exhibited robust JAK-STAT activation, indicating susceptibility to JAK inhibition with clinically approved agents, including upadacitinib. Exemplified by IFIM-driven inflammation, these findings identify pathogenic myeloid state remodeling as a molecular basis of anti-TNF resistance and provide a framework for mechanism-guided therapeutic strategies across chronic inflammatory diseases.

immunology↗

bioRxiv2021

Characterization of IL-22BP expression during Crohn's disease shows lack of evidence for IL-22BP production by T cells

Crohns disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.

immunology↗

bioRxiv2020

Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization

The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney (KTR) and hematopoietic stem cell transplant recipients. In KTR, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDC) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived DC (MDDC), an in vitro model for mDC, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDC. Endocytosed virions were efficiently transmitted to permissive cells and shown to be protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDC from the blood and kidney parenchyma behaved similarly to MDDC thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.

microbiology↗

bioRxiv2020

An easy and reliable whole blood freezing method for flow cytometry immuno- phenotyping and functional analyses

BackgroundImmune profiling by flow cytometry is not always possible on fresh blood samples due to time and/or transport constraints. Besides, the cryopreservation of peripheral blood mononuclear cells (PBMC) requires on-site specialized lab facilities, thus severely restricting the extent by which blood immune monitoring can be applied to multicenter clinical studies. These major limitations can be addressed through the development of simplified whole blood freezing methods. MethodsIn this report, we describe an optimized easy protocol for rapid whole blood freezing with the CryoStor(R) CS10 solution. Using flow cytometry, we compared cellular viability and composition on cryopreserved whole blood samples to matched fresh blood, as well as fresh and frozen PBMC. ResultsThough partial loss of neutrophils was observed, leucocyte viability was routinely >75% and we verified the preservation of viable T cells, NK cells, monocytes, dendritic cells and eosinophils in frequencies similar to those observed in fresh samples. A moderate decrease in B cell frequencies was observed. Importantly, we validated the possibility to analyze major intracellular markers, such as FOXP3 and Helios in regulatory T cells. Finally, we demonstrated good functional preservation of CS10-cryopreserved cells through the analysis of intracellular cytokine production in ex vivo stimulated T cells (IFNg, IL-4, IL-17A,) and monocytes (IL-1b, IL-6, TNFa). ConclusionsIn conclusion, our protocol provides a robust method to apply reliable immune monitoring studies to cryopreserved whole blood samples, hence offering new important opportunities for the design of future multicenter clinical trials.

immunology↗

bioRxiv2018

Immunological characterization of a rat model of Duchenne’s disease and demonstration of improved muscle strength after anti-CD45RC antibody treatment

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats (Dmdmdx) that closely reproduce the phenotype of DMD patients. Dmdmdx rats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4+ and CD8+ expressing high levels of CD45RChigh cells. Treatment of young Dmdmdx rats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RChigh T cells with no obvious side-effects. Prednisolone treatment of Dmdmdx rats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RChigh cells but resulted in severe weight loss.\n\nOverall, Dmdmdx rats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength in Dmdmdx rats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.

immunology↗