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Diabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease (DKD) is one of the most devastating complications, increasing the risk of death more than 10-fold over that in the general population [1]. Until very recently, the only drugs proven and recommended to slow progression of DKD were angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs), which act by inhibiting the renin-angiotensin system (RAS) [2]. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, RAS inhibitors have been grossly underutilized [3]. Moreover, even when RAS inhibitors are used, patients still have a high residual risk of DKD progression [1, 2]. Finally, the kidney-protective effect of RAS inhibitors has been categorically demonstrated only in patients with macro-albuminuria included in the IDNT and RENAAL trials – not in other individuals [4]. The lack of new therapies to treat DKD over the past two decades has therefore represented a tremendous challenge for patients and health care providers alike. selleck compound In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges and possible solutions to advance kidney health and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically-ill to SARS-CoV-2-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnC) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 Spike protein-1, increasing expression of viral entry proteins and reducing anti-viral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse β-coronavirus experienced increased senescence and inflammation with nearly 100% mortality. Targeting SnCs using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased anti-viral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality following viral infection, including SARS-CoV-2.Molecular mimicry is one of the leading mechanisms by which infectious agents can induce autoimmunity. Whether a similar mechanism triggers an antitumor immune response is unexplored, and the role of antiviral T cells infiltrating the tumor has remained anecdotal. To address these questions, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes. Using peptides identified by this tool, we demonstrated that, in mice, preexisting immunity toward specific viral epitopes enhanced the efficacy of cancer immunotherapy via molecular mimicry in different settings. To understand whether this mechanism could partly explain immunotherapy responsiveness in humans, we analyzed a cohort of patients with melanoma undergoing anti-PD1 treatment who had a high IgG titer for cytomegalovirus (CMV). In this cohort of patients, we showed that high levels of CMV-specific antibodies were associated with prolonged progression-free survival and found that, in some cases, peripheral blood mononuclear cells (PBMC) could cross-react with both melanoma and CMV homologous peptides. Finally, T-cell receptor sequencing revealed expansion of the same CD8+ T-cell clones when PBMCs were expanded with tumor or homologous viral peptides. In conclusion, we have demonstrated that preexisting immunity and molecular mimicry could influence the response to immunotherapies. In addition, we have developed a free online tool that can identify tumor antigens and neoantigens highly similar to pathogen antigens to exploit molecular mimicry and cross-reactive T cells in cancer vaccine development.Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, ANXA1 silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr172AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes.