New Viewpoint: Daniela Salvemini and Timothy Doyle (Saint Louis University) discuss the opportunity to target pro-inflammatory neuro-immune cell interactions in the treatment of neuropathic pain.
Ji-Hak Jeong, Shangwei Zhong, Jun-Li Luo (Scripps Research) and colleagues unveil that OBP2A from prostate cancer (PCa) in remission during androgen deprivation therapy enhances PCa growth and myeloid-derived suppressor cell infiltration through interaction with CXCL15/IL8, leading to castration-resistant PCa emergence. Targeting OBP2A of tumor in remission would be effective therapeutic strategy for advanced PCa.
Researchers at Memorial Sloan Kettering Cancer Center (MSKCC) in New York have discovered that common cancer treatments, such as radiotherapy or anthracycline drugs, cause long-term damage to heart tissue by activating a key inflammatory signaling pathway. The study, published today in the Journal of Experimental Medicine (JEM), suggests that inhibiting this pathway could reduce the chances of cancer survivors suffering heart disease later in life.
Original study: https://bit.ly/3Wt4L5L
Achraf Shamseddine, Suchit H. Patel, Adam M. Schmitt (Memorial Sloan Kettering Cancer Center) and colleagues show that DNA-damaging cancer therapies induce delayed activation of cGAS–STING-dependent type I interferon signaling in the heart. DNA damage–induced cGAS–STING signaling drives cardiac inflammation and late pathologic remodeling of the heart, progressive cardiac functional impairment, and late lethal cardiac toxicity.
🎥 See video summary by Suchit Patel: https://youtu.be/5aW4iEaCNdo
During influenza virus infection, Treg cell–derived amphiregulin is sensed by EGFR+Collagen-14+ lung mesenchymal cells, stimulating their activation and survival and supporting their role as signaling relay intermediates to promote effective alveolar regeneration. A new study from Katherine A. Kaiser, Nicholas Arpaia and colleagues (Columbia University):
Jaeu Yi and Chyi-Song Hsieh (Washington University in St. Louis) discuss work from Tanaka et al. (https://bit.ly/3FiEod5)
that advances our understanding of how genetic mutants that decrease T cell recognition of antigen, a critical event for immune activation to invading microbes and virus, paradoxically results in autoimmunity.
New Spotlight: In the mouse, γδIL17 cells are poised to make IL-17, and these cells have been involved in various infection and cancer models. Edwards et al. (https://bit.ly/3UCg7mH)
now report how different γδIL17 subsets are controlled during homeostasis and cancer. From Guillem Sanchez Sanchez and David Vermijlen (ULB - Université libre de Bruxelles):
Qiaoyun Chu, Jing An, Binghui Li and colleagues (Capital Medical University, Beijing) identify a clinical drug, nortriptyline, that can potently inhibit macropinocytosis-mediated fatty acid uptake, and further find that nortriptyline effectively suppresses tumor growth, lipogenesis, and hepatic steatosis in combination with ND-646, a selective ACC1/2 inhibitor.
Using epigenomics, transcriptomics, and functional studies, Rafael Han, Ilia Vainchtein, Anna Molofsky and colleagues (UCSF) define mechanisms through which interleukin-33 (IL-33) promotes microglial synapse engulfment during brain development and restricts seizure susceptibility, in part via the induction of pattern recognition receptors including the scavenger receptor MARCO.
Lévy, Gothe, Hauck, Béziat (Inserm) and colleagues show that Inherited CARMIL2 deficiency underlies infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation. CARMIL2 deficiency impairs CD28 signaling only partially in T cells but a comparison of CARMIL2 and CD28 deficiency in humans suggests that CARMIL2 governs immunological pathways beyond CD28.
Takuya Koike, Tomohiro Kurosaki, Wataru Ise et al. (Osaka University) employ a time-stamping method for plasma cells and measure the decay of homeostatic plasma cells with distinct isotypes, or antigen-specific plasma cells that are generated in germinal center–independent or –dependent pathways.
The underlying mechanisms that drive Th1 responses in the intestine remain unclear. Here, Fatemeh Ahmadi, William Agace and colleagues (Lund University) show that the microbiota-dependent post-weaning accumulation of Th1 cells in the intestine is dependent on cDC1 expression of MHC-II and IL-27.
We're pleased to present our annual Best of JEM series to highlight cutting-edge research in immunology, host-pathogen interactions, cancer biology, tumor immunology, cardiovascular biology, neuroscience and other areas published in 2022 at JEM. The top 10 papers are selected by the editorial team based, in part, on the number of requests for PDF and full-text HTML versions of an article in the first three months after publication. These studies represent the breadth of JEM’s scope and our longstanding interest in original findings in disease pathogenesis and therapy.
We would also like use this opportunity to thank our authors, reviewers and readers for your interest and continued support for JEM.
We hope you will enjoy this collection and encourage your feedback!
Takeshi Inoue, Tomohiro Kurosaki (Osaka University) and colleagues show that antibody feedback plays a role in generating Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees.
Sarah C. Edwards, Seth B. Coffelt (Cancer Research UK) and colleagues provide deep phenotypic analysis of mouse γδ T cells. They focus functional studies on IL-17A–producing γδ T cell subsets, showing that the co-inhibitory molecules, PD-1 and TIM-3, regulate cell expansion in tumor-bearing mice, which counteracts anti–PD-1 or anti–TIM-3 immunotherapy.
Postmortem microstructural studies together with in vivo magnetic resonance imaging show that human arachnoid granulations are porous channels that serve as transient filtration conduits for cerebrospinal fluid to flow directly into dural interstitial tissue, but not into venous sinuses.
New Insights from Jean-Leon Thomas (Institut du Cerveau - Paris Brain Institute) & Helene Benveniste discussing work from Shah et al. (https://bit.ly/3FpkP2T):