Immune cell profiling from pleural fluid offers prognostic value and potential targets in lung cancer: doi.org/10.1172/jci.insight.… This issue’s Cover features work by Khatri et al., reporting that macrophage reprogramming is associated with poor survival outcomes for patients with metastasis of #LungCancer to the pleural space. The cover image shows tumor-associated macrophages (CD163, red) surrounding an invading lung cancer metastatic lesion (pan-cytokeratin, green). Credit: Aaditya Khatri. @DukePACC @DukePulmFellows @CHESTFoundation

What if Mycobacterium tuberculosis couldn’t evade macrophage defenses? Campos et al. @UTSWMedCenter identify SMURF2 as a conserved negative regulator of selective autophagy that suppresses macrophage control of M. tuberculosis: doi.org/10.1172/jci.insight.… The figure shows increased phagosomal association in human macrophages exposed to the SMURF2 inhibitor Heclin. @the_asci #tuberculosis

Sunday Read💫: A novel axis that can fine-tune the immune response to glomerular and tubule cell damage: doi.org/10.1172/jci.insight.… Jamie R. Privratsky @JamiePrivratsky & team @DukeKidney @Duke_Anesthesia identify a novel myeloid cell-endothelial cell immunoregulatory axis, supporting a model whereby myeloid IL-1R1 activity constrains ER stress–mediated EBI3/IL27 secretion, thereby attenuating type I IFN expression in kidney endothelial cells and ameliorating autoimmune nephritis. The figure shows anti-IFNAR1 therapy abrogates kidney injury after NTS nephritis in mice lacking IL-1R1 specifically in myeloid cells (bottom); littermate controls (top). #AKI #Nephrology #kidney #macrophage

Saturday Highlight💫: Full-length macrophage TREM2 protects against atherosclerosis: doi.org/10.1172/jci.insight.… Tang et al. unravel the links between #Prediabetes, #CardiovascularDisease, and #HepaticSeatosis, identifying increased levels of soluble TREM2 in human subjects and preclinical models of prediabetes. Soluble, macrophage-derived TREM2 associated with plasma apolipoprotein C3, which in turn reduces clearance of triglyceride-rich lipoproteins and increases heart disease risk. Importantly, preservation of full length TREM2 in prediabetic, steatotic mice reduced dyslipidemia and atherosclerosis.

This study links faulty DNA repair to abnormal immune responses: doi.org/10.1172/jci.insight.… Yusuke Yamashita & team discover a partial defect in DNA repair weakens immune defenses yet promotes severe intestinal inflammation in a novel mouse model that recapitulates DNA-LIG4 syndrome. #DNARepair #Immunodeficiency #IntestinalInflammation

Transcriptomic profiling of immune cells in malignant pleural effusions identifies macrophage reprogramming associated with survival: doi.org/10.1172/jci.insight.…

Why does tuberculosis infection worsen HIV-1 outcomes? doi.org/10.1172/jci.insight.… Samantha Cronin, Gabriel Duette @_GabrielDuette et al. @WestmeadInst demonstrate that the TB-altered immune microenvironment enriches the presence of genetically intact virus and impairs CD8 T cell-mediated antiviral responses. These results may explain worsened outcomes for people coinfected with HIV-1 and TB. The accompanying image shows the experimental design to evaluate the effect of coculture of pleural effusions from patients with TB and CD8 T cells from people living with HIV. @_GabrielDuette #HIV #TB

An unexpected regulatory relationship reveals a therapeutic vulnerability in high-Wnt tumors: doi.org/10.1172/jci.insight.… Using pancreatic cancer models, David M. Virshup, Babita Madan & team @dukenus find that the cell-surface receptor EPHA2 cooperates with Wnt in the tumor environment to inhibit MAPK signaling. #CancerBiology #WntSignaling

Unraveling links between #Prediabetes, #CardiovascularDisease, and #HepaticSeatosis: doi.org/10.1172/jci.insight.… Tang et al. identified increased levels of soluble TREM2 in human subjects and preclinical models of prediabetes. Soluble, macrophage-derived TREM2 associated with plasma apolipoprotein C3, which in turn reduces clearance of triglyceride-rich lipoproteins and increases heart disease risk. Importantly, preservation of full length TREM2 in prediabetic, steatotic mice reduced dyslipidemia and atherosclerosis.

Saturday Spotlight💫: The role of SMOC2 in #KidneyFibrosis: doi.org/10.1172/jci.insight.… ✅ Several models of kidney injury ✅ Human biopsy samples ✅ In vitro assays to focus on a mechanistic pathway Casimiro Gerarduzzi @CasGerarduzzi & team describe a novel role for SMOC2 in promoting partial epithelial-to-mesenchymal transition and maladaptive repair mechanisms in renal tubular epithelial cells. @UMontreal @KidneyCanada @NSERC_CRSNG @CIHR_IRSC

Presenting a novel axis that can fine-tune the immune response to glomerular and tubule cell damage: Jamie R. Privratsky @JamiePrivratsky & team @DukeKidney @Duke_Anesthesia identify a novel myeloid cell-endothelial cell immunoregulatory axis, supporting a model whereby myeloid IL-1R1 activity constrains ER stress–mediated EBI3/IL27 secretion, thereby attenuating type I IFN expression in kidney endothelial cells and ameliorating autoimmune nephritis. The figure shows anti-IFNAR1 therapy abrogates kidney injury after NTS nephritis in mice lacking IL-1R1 specifically in myeloid cells (bottom); littermate controls (top). #AKI #Nephrology #kidney #macrophage

Mitochondrial gene therapy restores vision in a mouse model: doi.org/10.1172/jci.insight.… Cheng Ai @ai_cheng_zju Min-Xin Guan @MinxinGuan et al. @ZJU_China report allotopic expression of mitochondrial ND6 restored retinal and optic nerve function and improved vision in a mouse model of mitochondrial disease. The featured images show restored retinal cells and mitochondrial morphology after AAV2-ND6 treatment in mice. #MitochondrialDisease #GeneTherapy

Providing practical insights for the medical and scientific communities to support the next generation of physician-scientists: doi.org/10.1172/jci.insight.… Brian Thomas @bthomasZOU, Cynthia Y. Tang @_CynthiaTang et al. used publicly available data and a survey to identify barriers and challenges experienced during grant writing for dual-degree trainees across the nation. @DanielCBrock #PhysicianScientists