September 2015 | Volume 212, No. 10
Brief Definitive Report
- Cysteinyl leukotrienes mediate lymphokine killer activity induced by NKG2D and IL-15 in cytotoxic T cells during celiac disease
Tang et al. show that cytotoxic effector cells produce and respond to cysteinyl leukotrienes to allow target cell killing dependent on NKG2D and IL-15. They further demonstrate a role for cysteinyl leukotrienes in celiac disease pathogenesis.
- The pancreas anatomy conditions the origin and properties of resident macrophages
Calderon et al. define the origin, turnover, and functional characteristics of pancreatic macrophages at both the exocrine and endocrine sites under noninflammatory conditions.
- Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity
Expression of IKKα in intestinal epithelial cells promotes IL-22 production by group 3 innate lymphoid cells, and this axis is essential for defense against Citrobacter rodentium infection and to limit intestinal inflammation in response to DSS treatment.
- Brain endothelial TAK1 and NEMO safeguard the neurovascular unit
Ridder et al. show that deletion of NEMO, a component of NF-kB signaling, in brain endothelial cells results in increased cerebral vascular permeability and endothelial cell death, and recapitulates the neurological symptoms observed in the genetic disease incontinentia pigmenti.
- A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression
Giotopoulos et al. report a novel mouse model that closely mimics the natural progression of human chronic myeloid leukemia to blast crisis, and use this model to identify novel candidate genes and pathways that, in combination with BCR-ABL, drive disease progression.
- A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4–ERK5 axis
Wu et al. report a novel IL-17–mediated cascade via the IL-17R–TRAF4–ERK5 axis that directly stimulates keratinocyte proliferation and skin tumor formation in mice.
- Multicongenic fate mapping quantification of dynamics of thymus colonization
Ziętara et al demonstrate with multicongenic fate mapping that thymus seeding is directly restricted to the duration of niche occupancy rather than long-range effects.
- Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity
Paterson et al. demonstrate that, in contrast to CTLA-4 germline knockout mice, conditional deletion on T reg cells during adulthood confers protection from EAE and does not increase resistance to tumors.
- Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells
Sekiya et al. demonstrate that deletion of the nuclear orphan receptor Nr4a in T reg cells results in a fatal systemic immunopathology due to abrogated suppressive capability in limiting Th2 and Tfh conversion.
- Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome
Kolhatkar et al. report that altered BCR and TLR signaling orchestrates increased positive selection of transitional B cells expressing low-affinity self-reactive BCRs, leading to their enrichment within the naive B cell compartment. These findings have important implications to understand events that promote altered B cell selection in both Wiskott-Aldrich syndrome patients and in other autoimmune-prone individuals.
- Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation
Fiala et al. report that Kidins220/ARMS is a novel interactor of the B cell antigen receptor (BCR) and its deletion impairs B cell development and B cell functioning.
- Distinct germinal center selection at local sites shapes memory B cell response to viral escape
Local germinal center reactions that persist in the lung after influenza infection are required for the generation of cross-reactive memory B cells.
- NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1
NOS1−/− mice show reduced inflammatory responses and tissue damage in experimental sepsis models. Baig et al show that NOS1-derived NO production in macrophages leads to proteolysis of SOCS1 to alleviate its repression of NFkB transcriptional activity in response to TLR4-mediated responses.
- NK-DC crosstalk controls the autopathogenic Th17 response through an innate IFN-γ–IL-27 axis
DCs recruit NK cells to the draining lymph node where they interact with DC creating a positive feedback loop of IL-27 and IFNγ production, which is ultimately limited by IL-10. This innate NK-DC axis controls the development of the adaptive response and dampens induction of autoimmunity.