Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen
BACKGROUND Vaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODS We assessed serological responses to initial COVID-19 vaccination in baseline seronegative adults who received second-dose boosters in the ipsilateral or contralateral arm relative to initial vaccination. We measured serum SARS-CoV-2 spike–specific Ig, receptor-binding domain–specific (RBD-specific) IgG, SARS-CoV-2 nucleocapsid–specific IgG, and neutralizing antibody titers against SARS-CoV-2.D614G (early strain) and SARS-CoV-2.B.1.1.529 (Omicron) a...
Source: Journal of Clinical Investigation - March 16, 2024 Category: Biomedical Science Authors: Sedigheh Fazli, Archana Thomas, Abram E. Estrada, Hiro A.P. Ross, David Xthona Lee, Steven Kazmierczak, Mark K. Slifka, David Montefiori, William B. Messer, Marcel E. Curlin Source Type: research
Absence of Stat1 in donor CD4+ T cells promotes the expansion of Tregs and reduces graft-versus-host disease in mice
(Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Huihui Ma, Caisheng Lu, Judith Ziegler, Ailing Liu, Antonia Sepulveda, Hideho Okada, Suzanne Lentzsch, Markus Y. Mapara Source Type: research
TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase
Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Suowen Xu, Xiumei Wu, Sichen Wang, Mengyun Xu, Tingyu Fang, Xiaoxuan Ma, Meijie Chen, Jiajun Fu, Juan Guo, Song Tian, Tian Tian, Xu Cheng, Hailong Yang, Junjie Zhou, Zhenya Wang, Yanjun Yin, Wen Xu, Fen Xu, Jinhua Yan, Zhihua Wang, Sihui Luo, Xiao-Jing Zh Source Type: research
SGLT2 inhibitors: cardiorenal metabolic drugs for the ages
(Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Ralph A. DeFronzo Source Type: research
Autophagy differentially regulates tissue tolerance of distinct target organs in graft-versus-host disease models
Tissue-intrinsic mechanisms that regulate severity of systemic pathogenic immune-mediated diseases, such as acute graft-versus-host disease (GVHD), remain poorly understood. Following allogeneic hematopoietic stem cell transplantation, autophagy, a cellular stress protective response, is induced in host nonhematopoietic cells. To systematically address the role of autophagy in various host nonhematopoietic tissues, both specific classical target organs of acute GVHD (intestines, liver, and skin) and organs conventionally not known to be targets of GVHD (kidneys and heart), we generated mice with organ-specific knockout of ...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Katherine Oravecz-Wilson, Emma Lauder, Austin Taylor, Laure Maneix, Jeanine L. Van Nostrand, Yaping Sun, Lu Li, Dongchang Zhao, Chen Liu, Pavan Reddy Source Type: research
C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation
(Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Maggie E. Jones-Carr, Huma Fatima, Vineeta Kumar, Douglas J. Anderson, Julie Houp, Jackson C. Perry, Gavin A. Baker, Leigh McManus, Andrew J. Shunk, Paige M. Porrett, Jayme E. Locke Source Type: research
Tipping the balance toward transplantation tolerance: in vivo therapy using a mutated IL-2
Immune tolerance to allogenic transplanted tissues remains elusive, and therapeutics promoting CD4+FOXP3+ Tregs are required to achieve this ultimate goal. In this issue of the JCI, Efe and colleagues engineered an Fc domain fused to a human mutein IL-2 (mIL-2–Fc) bearing mutations that confer preferential binding to the high-affinity IL-2 receptor expressed on Tregs. In vivo mIL-2–Fc therapy effectively heightened mouse, monkey, and human Treg numbers, promoted tolerance to minor antigen mismatched skin grafts in mice, and synergized with immunosuppressive drugs used in the clinic. These findings warrant clinical tria...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Geoffrey Camirand, Fadi G. Lakkis Source Type: research
Targeting mitochondrial dynamics of morphine-responsive dopaminergic neurons ameliorates opiate withdrawal
Converging studies demonstrate the dysfunction of the dopaminergic neurons following chronic opioid administration. However, the therapeutic strategies targeting opioid-responsive dopaminergic ensembles that contribute to the development of opioid withdrawal remain to be elucidated. Here, we used the neuronal activity-dependent Tet-Off system to label dopaminergic ensembles in response to initial morphine exposure (Mor-Ens) in the ventral tegmental area (VTA). Fiber optic photometry recording and transcriptome analysis revealed downregulated spontaneous activity and dysregulated mitochondrial respiratory, ultrastructure, a...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Changyou Jiang, Han Huang, Xiao Yang, Qiumin Le, Xing Liu, Lan Ma, Feifei Wang Source Type: research
NETs unleashed: neutrophil extracellular traps boost chemotherapy against colorectal cancer
This study substantially advances our understanding of the multifaceted role of neutrophils and NETs in the outcome of anticancer treatment. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Alexandra Mousset, Jean Albrengues Source Type: research
A role for TMEM63 in the lung
Surfactants are essential for breathing. Although major progress has been made in the past half century toward an understanding of surfactant secretion mechanisms, the identity of the mechanosensor that couples breathing to surfactant secretion has remained elusive. In this issue of the JCI, Chen, Li, and colleagues provide evidence that the mechanosensor is the transmembrane 63 (TMEM63) ion channel. These findings open new avenues for future research into lung mechanobiology. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Jaime L. Hook Source Type: research
APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease
Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and G2 cause kidney disease is poorly understood. Here, we leveraged 3 experimental models and a recently reported small molecule blocker of APOL1 protein, VX-147, to identify the upstream mechanism of G1-induced cytotoxicity. In HEK293 cells, we demonstrated that G1-mediated Na+ import/K+ efflux triggered activation of GPCR/IP3–mediated calcium release from the ER, impair...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Somenath Datta, Brett M. Antonio, Nathan H. Zahler, Jonathan W. Theile, Doug Krafte, Hengtao Zhang, Paul B. Rosenberg, Alec B. Chaves, Deborah M. Muoio, Guofang Zhang, Daniel Silas, Guojie Li, Karen Soldano, Sarah Nystrom, Davis Ferreira, Sara E. Miller, Source Type: research
Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis
(Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Nidhi S. Dey, Sujai Senaratne, Vijani Somaratne, Nayani P. Madarasinghe, Bimalka Seneviratne, Sarah Forrester, Marcela Montes de Oca, Luiza Campos Reis, Srija Moulik, Pegine B. Walrad, Mitali Chatterjee, Hiro Goto, Renu Wickremasinghe, Dimitris Lagos, Pau Source Type: research
The etiologies of Kawasaki disease
Kawasaki disease (KD) is a systemic vasculitis that affects young children and can result in coronary artery aneurysms. The etiology is currently unknown, but new clues from the epidemiology of KD in Japan, the country of highest incidence, are beginning to shed light on what may trigger this acute inflammatory condition. Additional clues from the global changes in KD incidence during the COVID-19 pandemic, coupled with a new birth cohort study from Japan, point to the potential role of person-to-person transmission of an infectious agent. However, the rising incidence of KD in Japan, with coherent waves across the entire ...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Jane C. Burns Source Type: research
Single-cell deconvolution reveals high lineage- and location-dependent heterogeneity in mesenchymal multivisceral stage 4 colorectal cancer
Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in Union for International Cancer Control (UICC) stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analyzed the transcriptome of single cells derived from murine multivisceral CRC and delineated the intermetastatic cellular heterogeneity regarding tumor epithelium, stroma, and immune cells. Interestingly, we found an intercel...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Christopher Berlin, Bernhard Mauerer, Pierre Cauchy, Jost Luenstedt, Roman Sankowski, Lisa Marx, Reinhild Feuerstein, Luisa Schaefer, Florian R. Greten, Marina Pesic, Olaf Groß, Marco Prinz, Naomi Ruehl, Laura Miketiuk, Dominik Jauch, Claudia Laessle, An Source Type: research
Cancer neoepitopes viewed through negative selection and peripheral tolerance: a new path to cancer vaccines
A proportion of somatic mutations in tumors create neoepitopes that can prime T cell responses that target the MHC I–neoepitope complexes on tumor cells, mediating tumor control or rejection. Despite the compelling centrality of neoepitopes to cancer immunity, we know remarkably little about what constitutes a neoepitope that can mediate tumor control in vivo and what distinguishes such a neoepitope from the vast majority of similar candidate neoepitopes that are inefficacious in vivo. Studies in mice as well as clinical trials have begun to reveal the unexpected paradoxes in this area. Because cancer neoepitopes straddl...
Source: Journal of Clinical Investigation - March 1, 2024 Category: Biomedical Science Authors: Pramod K. Srivastava Source Type: research
