Correction: Peroxisome proliferator-activated receptor (PPAR)α expression in T cells mediates gender differences in deve...
...Published in The Journal of experimental medicine
Regulation of amyloid-β dynamics and pathology by the circadian clock.
Published in The Journal of experimental medicine
Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer's Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-am...
Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity.
...Published in The Journal of experimental medicine
Host-protective caspase-1 activity must be tightly regulated to prevent pathology, but mechanisms controlling the duration of cellular caspase-1 activity are unknown. Caspase-1 is activated on inflammasomes, signaling platforms that facilitate caspase-1 dimerization and autoprocessing. Previous studies with recombinant protein identified a caspase-...
Interleukin-10 stiffens the heart.
Published in The Journal of experimental medicine
Cardiac-resident macrophages are a diverse population of cells that have a critical role in the pathogenesis of heart failure. A new understanding of communication between macrophages and cardiac fibroblasts could lead to novel therapeutic strategies for heart failure with preserved ejection function.
Specifically differentiated T cell subset promotes tumor immunity over fatal immunity.
Published in The Journal of experimental medicine
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal gra...
A nonimmune function of T cells in promoting lung tumor progression.
Published in The Journal of experimental medicine
The involvement of effector T cells and regulatory T (T reg) cells in opposing and promoting solid organ carcinogenesis, respectively, is viewed as a shifting balance between a breach versus establishment of tolerance to tumor or self-antigens. We considered that tumor-associated T cells might promote malignancy via distinct mechanisms used by T ce...
A noncanonical function of cGAMP in inflammasome priming and activation.
...Published in The Journal of experimental medicine
Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STING) to...
USP1-UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses.
Published in The Journal of experimental medicine
Optimal activation of TANK-binding kinase 1 (TBK1) is crucial for initiation of innate antiviral immunity and maintenance of immune homeostasis. Although several E3 ubiquitin ligases have been reported to regulate TBK1 activation by mediating its polyubiquitination, the functions of deubiquitinase on TBK1 activity remain largely unclear. Here, we i...
Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects.
...Published in The Journal of experimental medicine
The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pr...
A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis....
...Published in The Journal of experimental medicine
The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory di...
