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Issues

ISSN 0022-1007
EISSN 1540-9538
In this Issue

Insights

Huynh et al. and Yu et al. demonstrate that the transcription factor Bhlhe40 acts is a repressor of IL-10 production during infection with Mycobacterium tuberculosis or Toxoplasma gondii. Deletion of Bhlhe40 in both cases resulted in chronic infection and increased pathogen load as a consequence of increased IL-10 production.

A20 and its binding partner ABIN-1 are genetically linked to inflammatory diseases. In this issue of JEM, Kattah et al. demonstrate that simultaneous deletion in a mouse model leads to instantaneous cell death in the intestinal epithelium and mortality.

The precise downstream mediators of TGF-β signaling in Th17 and T reg cells remain unclear. In this issue of JEM, Tanaka et al. report that Trim33 transduces TGF-β signals in Th17 cells to generate an optimal proinflammatory cytokine profile.

Review

Viruses mimic histone proteins to gain control over gene regulatory networks, maximize replication, and suppress host antiviral immunity.

Brief Definitive Report

Norris et al. show that microglia are the key phagocytes in removal of synaptic debris in the dorsal lateral geniculate nucleus after optic nerve injury. This microglial function is dependent on recognition of neurodegeneration and is mediated by the complement system.

Effector CD4 T cells with progenitor properties are present during chronic intestinal inflammation, and these cells support the maintenance of disease. The expression of the glycosyltransferase ST6Gal-I by these cells promotes cell survival and TCF1 levels.

The balance between inflammatory IFN-γ and antiinflammatory IL-10 plays a critical role in modulating type 1 immune responses. Yu et al. show that the transcription factor Bhlhe40 serves as a molecular switch between inflammatory and antiinflammatory Th1 cells.

Article

This study demonstrates that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) is essential during Mycobacterium tuberculosis infection to specifically regulate Il10 expression, revealing the importance of strict control of IL-10 production by innate and adaptive immune cells during infection.

A20 (TNFAIP3) and ABIN-1 (TNIP1), two candidate inflammatory bowel disease (IBD) susceptibility genes, preserve intestinal homeostasis by cooperatively restricting intestinal epithelial cell death. A20 and ABIN-1 synergistically restrict both TNF-dependent and TNF-independent cell death.

Trim33, a modulator of TGF-β signaling, mediates the proinflammatory function of Th17 cells by the promotion of IL-17 and repression of IL-10 production. These cytokine expressions are regulated through an epigenetic mechanism in cooperation with Smad2 and ROR-γ.

Moalli et al. combine in vitro CD8+ T cell motility analysis with intravital imaging of mouse tissues to identify the actomyosin regulator Myo9b as a central player for nonlymphoid tissue infiltration during adaptive immune responses by facilitating crossing of tissue barriers.

Chemotherapy-resistant dormant colorectal cancer cells are a differentiated cell that can de-differentiate and proliferate, accounting for tumor recurrence. Itraconazole induces all tumor cells, including those dormant, to proliferate then enter senescence and is effective in multiple preclinical assays.

Adaptive responses have been demonstrated to limit activity to targeted therapies. Saei et al. show that loss of USP28/FBW7-mediated BRAF degradation is observed in a proportion of melanoma patients and can be responsible for resistance through upregulation of MAPK signaling pathway.

Mansour et al. demonstrate that JDP2, a bZIP transcription factor, is overexpressed in patients with high-risk T cell acute lymphoblastic leukemia (T-ALL). JDP2 initiates T-ALL in a zebrafish model and leads to steroid resistance in vivo through direct regulation of MCL1.

Jensen et al. report the identification and characterization of novel lymphoid progenitor populations in the mouse bone marrow. The work resolves the complexity of the BLP/pre-pro–B/Fraction A compartments and provides a developmental trajectory for early B cell development.

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