Follicular regulatory T cells promote experimental autoimmune encephalomyelitis by supporting B cell egress from germinal centers.

Follicular regulatory T cells (T cells) constitute a subset of regulatory T cells pivotal to the immune response in germinal centers (GCs) that inhibit autoantibody production. Their role, however, remains ill-defined in autoimmune diseases like multiple sclerosis (MS) and its murine model, experimental autoimmune encephalomyelitis (EAE), which are neuroinflammatory diseases driven by T and B cells. Here, we quantified peripheral blood immune subpopulations in two cohorts of patients with MS and found higher circulating T cell frequencies in patients in relapse compared with patients in remission.

Durable B-Cell Impairment While Sparing IgA B Cells After Ocrelizumab Therapy in Multiple Sclerosis.

Objectives: Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular B-cell profiles in patients prior to OCR treatment, on OCR treatment, and after 15 months of therapy discontinuation. This study aims to provide new clues about the mechanisms of action of OCR and about disease pathophysiology.

Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution.

Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.

Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.

Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis.

Corrigendum: Follicular lymphoma regulatory T-cell origin and function.

[This corrects the article DOI: 10.3389/fimmu.2024.

Follicular lymphoma regulatory T-cell origin and function.

Introduction: Follicular Lymphoma (FL) results from the malignant transformation of germinal center (GC) B cells. FL B cells display recurrent and diverse genetic alterations, some of them favoring their direct interaction with their cell microenvironment, including follicular helper T cells (Tfh). Although FL-Tfh key role is well-documented, the impact of their regulatory counterpart, the follicular regulatory T cell (Tfr) compartment, is still sparse.

Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature.

Background And Objectives: Tertiary lymphoid structures and aggregates are reported in the meninges of patients with multiple sclerosis (MS), especially at the progressive stage, and are strongly associated with cortical lesions and disability. Besides B cells, these structures comprise follicular helper T (Tfh) cells that are crucial to support B-cell differentiation. Tfh cells play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases, but very few are known in MS.

Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.

Intrauterine growth restriction (IUGR) is associated with reduced kidney size at birth, accelerated renal function decline, and increased risk for chronic kidney and cardiovascular diseases in adults. Precise mechanisms underlying fetal programming of adult diseases remain largely elusive and warrant extensive investigation. Setting up a mouse model of hypoxia-induced IUGR, fetal adaptations at mRNA, protein and cellular levels, and their long-term functional consequences are characterized, using the kidney as a readout.

Human Lymphoid Stromal Cells Contribute to Polarization of Follicular T Cells Into IL-4 Secreting Cells.

Fibroblastic reticular cells (FRCs) are the specialized lymphoid stromal cells initially identified as triggering T-cell recruitment and dynamic motion in secondary lymphoid organs. Interestingly, FRCs also display antigen presentation capacities and support lymphocyte survival. CXCR5CD4 follicular T cells are important players of B-cell maturation and antibody response.

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response.

During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses.

Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis.

Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice.

Background: Intrauterine growth restriction (IUGR) occurs in up to 10% of pregnancies and is considered as a major risk to develop various diseases in adulthood, such as cardiovascular diseases, insulin resistance, hypertension or end stage kidney disease. Several IUGR models have been developed in order to understand the biological processes linked to fetal growth retardation, most of them being rat or mouse models and nutritional models. In order to reproduce altered placental flow, surgical models have also been developed, and among them bilateral uterine ligation has been frequently used.

Phosphatase and tensin homolog regulates stability and activity of EphB1 receptor.

Deregulation of receptor tyrosine kinases (RTKs) is linked to a broad range of cancers, stressing the necessity of studying their regulatory pathways. We and others demonstrated previously that c-Cbl is necessary for the lysosomal degradation of erythropoietin-producing hepatocellular B1 (EphB1) carcinoma and epidermal growth factor receptor (EGFR) RTKs. Moreover, the tumor suppressor phosphatase and tensin homolog (PTEN) was shown to modulate c-Cbl-dependent EGFR degradation.

The Role of PTEN in Tumor Angiogenesis.

During the past 20 years, the phosphatase and tensin homolog PTEN has been shown to be involved in major physiological processes, and its mutation or loss is often associated with tumor formation. In addition PTEN regulates angiogenesis not only through its antagonizing effect on the PI3 kinase pathway mainly, but also through some phosphatase-independent functions. In this paper we delineate the role of this powerful tumor suppressor in tumor angiogenesis and dissect the underlying molecular mechanisms.

In vivo major histocompatibility complex class I (MHCI) expression on MHCIlow tumor cells is regulated by gammadelta T and NK cells during the early steps of tumor growth.

Cell surface expression of MHC class I molecules by tumor cells is determinant in the interplay between tumor cells and the immune system. Nevertheless, the mechanisms which regulate MHCI expression on tumor cells are not clear. We previously showed that immune innate cells from the spleen can regulate MHCI expression on MHCI(low) tumor cells.