Nature Immunology, Published online: 15 April 2021; doi:10.1038/s41590-021-00918-0The TAM receptor kinases Axl and Mer are critical for microglial recognition and clearance of accumulating amyloid in transgenic models of Alzheimer’s disease.
Nature Immunology, Published online: 15 April 2021; doi:10.1038/s41590-021-00890-9Ulrich von Andrian recounts how an unexpected experimental result called into question a well-established concept in immunology: the mechanism of immune memory. Follow-up experiments revealed that NK cells can mediate antigen-specific adaptive immune responses.
Nature Immunology, Published online: 15 April 2021; doi:10.1038/s41590-021-00913-5How microglia sense amyloid plaques in Alzheimer’s disease has remained mysterious. Lemke and colleagues report that TAM receptor kinases are absolutely required for normal microglial recognition of, response to and phagocytosis of Aβ plaques. Surprisingly, TAM-mediated microglial phagocytosis of Aβ material does not constrain, but rather promotes, the formation of dense-core plaques.
Nature Immunology, Published online: 15 April 2021; doi:10.1038/s41590-021-00909-1Sun and colleagues provide a new resource, multi-omics analysis of NK cell Jak–STAT signaling in response to the cytokines IL-2, IL-15, IL-12, IL-18 and IFN-α, showing synergistic and antagonistic interactions that govern NK cell activity.
Nature Immunology, Published online: 13 April 2021; doi:10.1038/s41590-021-00919-zThe COVID-19 response in Greece has been swift and flexible, adapting to the evolving pandemic and creating unique opportunities for research.
Nature Immunology, Published online: 12 April 2021; doi:10.1038/s41590-021-00915-3Katharina Gaus 1972–2021
Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4<sup>+</sup> T cell perturbations
Nature Immunology, Published online: 08 April 2021; doi:10.1038/s41590-021-00910-8FOXP3 deficiency leads to dramatic loss of immune homeostasis. This multicenter collaborative group finds that loss of FOXP3 function only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs Treg cells.
Nature Immunology, Published online: 31 March 2021; doi:10.1038/s41590-021-00903-7Viral pathogens frequently target host cell antigen-processing pathways, including MHC-I–TAP peptide transporters, to evade host immunity. Blander and colleagues describe how MHC-I molecules can still cross-present antigen by re-routing ERGIC-resident MHC molecules to phagosomal vesicles, where phagolysosomal proteases act to shape the peptide repertoire for MHC-I presentation.
Nature Immunology, Published online: 29 March 2021; doi:10.1038/s41590-021-00912-6Nilabh Shastri 1952–2021
Publisher Correction: Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<sub>H</sub> archetypes
Nature Immunology, Published online: 26 March 2021; doi:10.1038/s41590-021-00916-2Publisher Correction: Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
Nature Immunology, Published online: 26 March 2021; doi:10.1038/s41590-021-00908-2Taiwan has leveraged its experience in containing the 2003 SARS outbreak by responding to the COVID-19 crisis with rapid measures, early deployment, prudent actions and transparency. Collectively, these actions have created the ‘Taiwan model’ for combating COVID-19.
Nature Immunology, Published online: 25 March 2021; doi:10.1038/s41590-021-00881-wHIV-1 infection of CD4+ T cells triggers the interaction of the mitochondrial proteins NLRX1 and FASTKD5 to promote oxidative phosphorylation, leading to increased viral replication. It has now been shown that this process can be blocked by metformin.
Nature Immunology, Published online: 25 March 2021; doi:10.1038/s41590-021-00888-3The E3 ubiquitin ligase MDM2 inhibits the tumor suppressor p53 and is an important therapeutic target. Zou and colleagues demonstrate that MDM2 also has a T cell-intrinsic role that supports antitumor responses.
Multi-omics analyses reveal that HIV-1 alters CD4<sup>+</sup> T cell immunometabolism to fuel virus replication
Nature Immunology, Published online: 25 March 2021; doi:10.1038/s41590-021-00898-1Ting and colleagues use multi-omics to examine the alterations undergone by CD4+ T cells following HIV-1 infection. They describe mechanistic changes that lead to elevated oxidative phosphorylation, which, if inhibited, leads to suppression of HIV-1 infection.
Nature Immunology, Published online: 25 March 2021; doi:10.1038/s41590-021-00896-3Sharma and colleagues identify the kinase DAPK3 as a positive regulator of the STING–interferon-β activation pathway. DAPK3 acts to modify E3 ubiquitin ligases that regulate STING K63-linked poly-ubiquitination.
Nature Immunology, Published online: 23 March 2021; doi:10.1038/s41590-021-00905-5The eradication of pathogens and establishment of immunological memory depend on the generation of both effector and long-lived memory cells within specialized immune niches. Whole-organ imaging demonstrates that, during viral infection, the fate of CD8+ T cells in lymph nodes is coupled to chemotactic signals controlling their distribution within different microanatomical sites.
Nature Immunology, Published online: 22 March 2021; doi:10.1038/s41590-021-00904-6In the colonic environment, sustained Wnt–β-catenin activation in regulatory T cells promotes epigenetic rewiring toward proinflammatory RORγt+ Treg cells, whose expansion parallels the disease progression from inflammatory bowel disease (IBD) to manifest colorectal cancer (CRC).
Nature Immunology, Published online: 22 March 2021; doi:10.1038/s41590-021-00893-6Riok2 haploinsufficiency leads to aberrant TH22 skewing and interleukin-22-mediated erythroid dysfunction.
Nature Immunology, Published online: 22 March 2021; doi:10.1038/s41590-021-00895-4Growing evidence suggests that immune dysregulation is involved in the pathogenesis of myelodysplastic syndromes (MDSs). Glimcher and colleagues report haplosufficiency of the serine–threonine kinase RIOK2 leads to increased IL-22 production that, in turn, suppresses erythropoiesis. Blocking IL-22 rescues this defect in mice, suggesting that IL-22 blockade might be of therapeutic value in treating MDSs.
Nature Immunology, Published online: 22 March 2021; doi:10.1038/s41590-021-00899-0Extracellular vesicles (EVs) can exert potent immunomodulatory effects. Wirtz and colleagues review the types of EV and their influence on tumor responses.