CD8 Regulatory T Cells Induced by Peptide Vaccination Ameliorates Experimental Model of Membranous Nephropathy.

Aim: CD8 regulatory T cells (Tregs) are cross-protective across multiple animal models of autoimmunity. Recently, specific peptides from a yeast-peptide-major histocompatibility complex library that expanded CD8 Tregs in murine experimental multiple sclerosis were reported. Whether these peptides also expand CD8 Tregs and protect against Heymann nephritis (HN), an experimental model of membranous nephropathy is unknown.

T cell costimulatory blockade ameliorates induction of experimental membranous nephropathy potentially through T-helper 17 cell suppression in the kidney.

Background And Hypothesis: Recent advances in membranous nephropathy treatment have focused on B cell depletion, which is incompletely effective, potentially due to persistent autoantibody-producing plasma cells or alternative pathways of injury. T cell costimulatory blockade (cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4)-Ig) to prevent T cell-dependent B cell activation and short-course proteasome inhibition (bortezomib) to deplete plasma cells may represent a complementary form of treatment.

Methods: Lewis rats were immunized with Fx1A and complete Freund's adjuvant (CFA) to induce experimental membranous nephropathy (Heymann nephritis or HN) and treated with CTLA4-Ig alone or CTLA4-Ig plus a short-course of bortezomib.

Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol.

Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems.

Perspectives of Caregivers on Access to Health Care for Children with CKD.

Introduction: Inequitable access to health care based on demographic factors such as ethnicity, socioeconomic status and geographical location has been consistently found in children with chronic kidney disease (CKD). However, little is known about the perspectives of caregivers on accessing health care. We described caregivers' perspectives on accessing health care for children with CKD from socioeconomically disadvantaged backgrounds and/or rural or remote areas.

Patient, Parental, and Health Professional Perspectives on Growth in Children With CKD.

Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study describes the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals.

Intragraft memory-like CD127hiCD4+Foxp3+ Tregs maintain transplant tolerance.

CD4+Foxp3+ regulatory T cells (Tregs) play an essential role in suppressing transplant rejection, but their role within the graft and heterogeneity in tolerance are poorly understood. Here, we compared phenotypic and transcriptomic characteristics of Treg populations within lymphoid organs and grafts in an islet xenotransplant model of tolerance. We showed Tregs were essential for tolerance induction and maintenance.

Graft-versus-leukaemia immunity is retained following treatment with post-transplant cyclophosphamide alone or combined with tocilizumab in humanised mice.

Objectives: Donor haematopoietic stem cell transplantation treats leukaemia by inducing graft-versus-leukaemia (GVL) immunity. However, this benefit is often mitigated by graft-versus-host disease (GVHD), which is reduced by post-transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity.

Foxp1 Is Required for Renal Intercalated Cell Differentiation and Acid-Base Regulation.

Key Points: Foxp1 is a key transcriptional factor for the differentiation of intercalated cells in collecting ducts. Dmrt2 and Hmx2 act downstream of Foxp1 to control the differentiation of type A and type B intercalated cells, respectively. Foxp1 and Dmrt2 are essential for body acid–base balance regulation.

The Concise Guide to PHARMACOLOGY 2023/24: Transporters.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

The Concise Guide to PHARMACOLOGY 2023/24: Catalytic receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

The Concise Guide to PHARMACOLOGY 2023/24: Enzymes.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.

The Concise Guide to PHARMACOLOGY 2023/24: Nuclear hormone receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

The IUPHAR/BPS Guide to PHARMACOLOGY in 2024.

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; https://www.guidetopharmacology.org) is an open-access, expert-curated, online database that provides succinct overviews and key references for pharmacological targets and their recommended experimental ligands.

Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury.

Background And Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI).

Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI.

Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation.

Purpose: To assess the relative cost-effectiveness of genomic testing compared with standard non-genomic diagnostic investigations in patients with suspected monogenic kidney disease from an Australian health care system perspective.

Methods: Diagnostic and clinical information was used from a national cohort of 349 participants. Simulation modelling captured diagnostic, health, and economic outcomes during a time horizon from clinical presentation until 3 months post-test results based on the outcome of cost per additional diagnosis and lifetime horizon based on cost per quality-adjusted life-year (QALY) gained.

Advances in malaria pharmacology and the online guide to MALARIA PHARMACOLOGY: IUPHAR review 38.

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies.