: Medicine Articles
Letter: The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccinationAn ideal vaccination strategy against tumors relies on specific antigens that are required for tumor maintenance. For lymphoma, vaccination with subject-specific immunoglobulin idiotypes has had the most promising results. Here we show that DNA vaccination with plasmids encoding portions of the cytoplasmic domain of anaplastic lymphoma kinase (ALK), which has been translocated in different fusion proteins necessary for the growth of anaplastic large cell lymphoma (ALCL), protects mice from local and systemic lymphoma growth. The protection is potent and long lasting and elicits ALK-specific interferon-γ responses and CD8+ T cell–mediated cytotoxicity. A combination of chemotherapy and vaccination significantly enhanced the survival of mice challenged with ALK+ lymphomas. These findings indicate that ALK represents an ideal tumor antigen for vaccination-based therapies of ALCL and possibly other ALK+ human tumors. Nature Medicine, vol. 14 #6, pp676-680 |
Letter: Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathologyAlzheimer's disease is the most common dementia and is pathologically characterized by deposition of amyloid-β peptide (Aβ) into β-amyloid plaques, neuronal injury and low-level, chronic activation of brain immunity. Transforming growth factor-βs (TGF-βs) are pleiotropic cytokines that have key roles in immune cell activation, inflammation and repair after injury. We genetically interrupted TGF-β and downstream Smad2/3 signaling (TGF-β–Smad2/3) in innate immune cells by inducing expression of CD11c promoter–driven dominant-negative TGF-β receptor type II in C57BL/6 mice (CD11c-DNR), crossed these mice with mice overexpressing mutant human amyloid precursor protein, the Tg2576 Alzheimer's disease mouse model, and evaluated Alzheimer's disease-like pathology. Aged double-transgenic mice showed complete mitigation of Tg2576-associated hyperactivity and partial mitigation of defective spatial working memory. Brain parenchymal and cerebrovascular β-amyloid deposits and Aβ abundance were markedly (up to 90%) attenuated in Tg2576–CD11c-DNR mice. This was associated with increased infiltration of Aβ-containing peripheral macrophages around cerebral vessels and β-amyloid plaques. In vitro, cultures of peripheral macrophages, but not microglia, from CD11c-DNR mice showed blockade of classical TGF-β–activated Smad2/3 but also showed hyperactivation of alternative bone morphogenic protein–activated Smad1/5/8 signaling and increased Aβ phagocytosis. Similar effects were noted after pharmacological inhibition of activin-like kinase-5, a type I TGF-β receptor. Taken together, our results suggest that blockade of TGF-β–Smad2/3 signaling in peripheral macrophages represents a new therapeutic target for Alzheimer's disease. Nature Medicine, vol. 14 #6, pp681-687 |
News and Views: Multiple layers of metabolismA new layer of gene regulation emerges for the metabolic regulator peroxisome proliferator–activated receptor-δ (PPAR-δ). A team consisting of a Krüppel-like transcription factor and a SUMO protease regulate the expression of PPAR-δ target genes, thereby controlling energy metabolism (pages 656–666). Nature Medicine, vol. 14 #6, pp603-604 |
News and Views: Lung NKT cell commotion takes your breath awayInfectious agents can induce inflammatory lung disease akin to asthma and chronic obstructive pulmonary disease. Work in a new mouse model provides mechanistic insight into this process and uncovers a key role for invariant natural killer T cells (pages 633–640). Nature Medicine, vol. 14 #6, pp609-610 |
News and Views: Bench to Bedside: Betting on B cells in multiple sclerosisA variety of immune cell types contribute to disease in individuals with multiple sclerosis, an autoimmune condition of the central nervous system. Thomas Prod'homme and Scott Zamvil comment on the 'Bench to Bedside' approach, examining how recent basic research implicates the antigen-presenting cell in this disease. In our 'Bedside to Bench' column, Hans Link explores how recent clinical trials may bolster a mechanistic role for the B cell. Nature Medicine, vol. 14 #6, pp615-616 |
News and Views: The long reach of leptinThe energy-regulating hormone leptin affects signals emerging from certain brain regions. New results explore the nature of these signals, finding a central role for phosphoinositide-3 kinase in the brain and the endocannabinoid system in adipocytes (pages 667–675). Nature Medicine, vol. 14 #6, pp604-606 |
News and Views: Bench to Bedside: Tempering antigen-presenting cells in multiple sclerosisA variety of immune cell types contribute to disease in individuals with multiple sclerosis, an autoimmune condition of the central nervous system. Thomas Prod'homme and Scott Zamvil comment on the 'Bench to Bedside' approach, examining how recent basic research implicates the antigen-presenting cell in this disease. In our 'Bedside to Bench' column, Hans Link explores how recent clinical trials may bolster a mechanistic role for the B cell. Nature Medicine, vol. 14 #6, pp614-615 |
News and Views: Keeping blood clots at bay in sepsisClearance of platelets by the liver can help counteract the dangerous blood coagulation that can occur during sepsis. The mechanism involves clearance of platelets through the liver's Ashwell receptor, which binds to platelet glycoproteins altered by sepsis-causing bacteria (pages 648–655). Nature Medicine, vol. 14 #6, pp606-608 |
News and Views: Gilbert Ashwell: sweet on scienceIn 1974, Gilbert Ashwell and Anatol Morell discovered a receptor in the liver that recognizes particular glycoproteins, dubbed asialoglycoproteins. We asked Ashwell about his discoveries and what he thinks of the study by Grewal et al. in this issue, which suggests that the receptor is involved in regulating sepsis. Nature Medicine, vol. 14 #6, pp608-608 |