Newest Articles
Regulation of amyloid-β dynamics and pathology by the circadian clockCircadian dysfunction is common in Alzheimer’s disease, but its role in disease pathogenesis is unknown. Kress et al. demonstrate that the circadian clock regulates daily rhythms in amyloid-β and that genetic disruption of clock function accelerates amyloid plaque accumulation in mice.
Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infectionNair et al. define a key role for Irg1 in minimizing the pathological immune response associated with Mtb infection. Using Irg1−/− and Irg1fl/fl conditional mice, detailed immune cell analysis, and transcriptional profiling, their data supports a model where Irg1 expression in myeloid cell subsets tempers inflammation and controls the recruitment and infection of neutrophils during Mtb infection.
Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activationCarpier et al. show that LAT trafficking to the immune synapse depends on endosome-to-Golgi/TGN retrograde transport and is controlled by Rab6 and Syntaxin-16. Moreover, they show that this retrograde pathway controls the TCR-induced activation of T lymphocytes.
STAT-3–independent production of IL-17 by mouse innate-like αβ T cells controls ocular infectionSt. Leger et al. identify and examine innate-like αβ T cells that circumvent canonical STAT-3 phosphorylation to produce protective IL-17. These cells can exist in the ocular mucosa and protect the ocular surface from pathogenic Staphylococcus aureus infection.
Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cellsPlasmablasts generated in germinal centers (GC) emerge at the GC–T zone interface (GTI). Zhang et al. demonstrate two major regulators of this process: Tfh-derived IL-21 and APRIL produced by CD157high fibroblastic reticular cells located in the GTI.
ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fatesGuan et al. identify genetic cooperativity between the transcription factor ZEB1 and the miR-200 family in memory CD8+ T cell development, which contrasts with that observed in the EMT. This study also shows that ZEB1 and its closely related homologue, ZEB2, play functionally distinct roles in CD8+ T cell differentiation.
ADAM17 is required for EGF-R–induced intestinal tumors via IL-6 trans-signalingSchmidt et al. show that loss of the membrane-bound metalloprotease ADAM17 led to impaired intestinal cancer development in the murine APCmin/+ model, which also depended on IL-6 trans-signaling via the soluble IL-6R and could be blocked by the specific IL-6 trans-signaling inhibitor sgp130Fc.
4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responsesTumor-infiltrating T cells experience metabolic repression that hinders their function and thus response to immunotherapy. Menk et al. show that ligation of 4-1BB, a TNFR family costimulatory molecule, can promote increased metabolic sufficiency, which enables intratumoral T cell function and response to immunotherapy.
ApoE facilitates the microglial response to amyloid plaque pathologyIncreasing evidence suggests that apoE influences the innate immune response in neurodegeneration. Here, Ulrich et al. report that apoE influences amyloid plaque morphology and the microglial response to amyloid plaques, along with plaque-associated neuronal toxicity.
Primary atopic disordersImportant insights from monogenic disorders into the immunopathogenesis of allergic diseases and reactions are discussed.