In this issue of JEM, Sundaram et al. report a mechanism by which the normal epithelial wound healing response is “hijacked” to promote invasion and metastasis in head and neck squamous carcinomas (HNSCCs), a finding that unveils new markers of poor outcomes and potential targets for therapeutic intervention.
Perlin et al. discuss recent findings in the field of zebrafish hematopoiesis, focusing on the transcriptional regulation of hematopoietic stem cell (HSC) induction and HSC–niche interactions. Manipulation of developmental signaling pathways may enhance HSC bioengineering, which would improve transplantation therapies.
Brief Definitive Report
Mossadegh-Keller et al. show distinct origin of two different testicular macrophage populations during the postnatal development. Embryonic precursors give rise exclusively to the interstitial macrophage population, whereas peritubular macrophages derive from bone marrow progenitors only postnatally. Surprisingly, both macrophage populations display a remarkable long life span.
Zhu et al. show that the Zika virus, which has a tropism for fetal and adult neuroprogenitor cells, targets and kills cancer stem cells while leaving differentiated tumor cells relatively unaffected, providing a new potential oncolytic virus therapy in neuro-oncology.
This study by Khrimian et al. demonstrates that the bone-derived hormone osteocalcin is necessary and sufficient to correct age-related cognitive decline in the mouse. It also provides genetic, molecular, and neurophysiological evidence that Gpr158 is the receptor mediating osteocalcin’s regulation of cognition.
Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing
The work by Tang et al. provides a comprehensive, single-cell, transcriptomic analysis of kidney and blood cells from the adult zebrafish, identifying novel cell types, including two classes of NK immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells.
Exploring the parallels between wound healing and epithelial cancers, Sundaram et al. elucidate the mechanism by which cancer cells hijack the wound healing switch to enhance invasion and metastasis in head and neck squamous cell carcinoma.
Tanaka et al. show that BCL6 corepressor (BCOR) targets a significant portion of NOTCH1 targets in thymocytes to restrain their activation. Conditional deletion of the BCL6-binding domain of BCOR results in induction of Notch-dependent acute T-cell lymphoblastic leukemia in mice.
Zens et al. demonstrate a deficiency in the establishment of protective lung tissue-resident memory T cells following respiratory infection during infancy that is T cell intrinsic and can be ameliorated by reduced expression of T-bet during infection. These findings reveal a potential mechanism for increased susceptibility to infection in infancy and identify T-bet as a mediator of TRM generation in early life.
Tenno et al. show that loss of Cbfβ2, one of two RNA splice variants of the Cbfb gene, results in the persistence of embryonic Langerhans cell precursors in the adult epidermis by selective loss of BMP7-BMPR1A signaling with intact TGFβR1 signaling.
Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation
Kang et al. showed that reduced vaccinia-related kinase 3 (VRK3) expression affects synaptic structure and function and results in cognitive dysfunction and autism-like behaviors in mice. TrkB stimulation reverses the altered synaptic properties and restores autism-like behaviors in VRK3-deficient mice.
Kollek et al. show that transient inhibition of apoptosis by short-term BCL-XL overexpression increases the viability of hematopoietic stem cells (HSCs) during engraftment and improves the outcome of HSC transplantation without signs of adverse pathologies. This strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.
Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation
Hosomi et al. show that intestinal epithelial cell–specific deletion of X-box–binding protein 1, an unfolded protein response–related transcription factor, results in CHOP-dependent increased expression of specific natural killer group 2 member D (NKG2D) ligands. This activates NKG2D-expressing intraepithelial group 1 ILCs and promotes small intestinal inflammation.
Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells
Villarino et al. demonstrate that STAT5 is required for accumulation and function of all ILC subsets in mice. They also define a STAT5-driven transcriptional signature in NK cells and reveal a cooperative relationship with T-bet, another key ILC transcription factor.
PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation
Nobs et al. show that PPARγ drives pathogenic type-2 effector responses in the lung in both T cells and DCs by controlling IL-33–driven Th2 effector function and lung DC migration and Th2 priming capacity.
Ito et al. show that IL-22, which is produced mainly by CD4+ T cells, induces Reg3γ expression from lung epithelial cells through STAT3 activation and suppresses allergic airway inflammation via the inhibition of epithelial cytokine production.
LRRK2 is a serine/threonine protein kinase previously implicated in immunity against intracellular pathogens. In this study, Liu et al. report that LRRK2 promotes the host defense against Salmonella Typhimurium infection by phosphorylating NLRC4 at Ser533, thereby promoting the activation of NLRC4 inflammasome.
NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome
The microenvironment, including microbial products, plays a role in mature B cell survival. Hayakawa et al. show that B cell antigen receptor ligand–mediated Nod1 up-regulation in vivo in B cell development leads to preferential mature B cell survival as a competitive survival, increasing the Nod1+ B cell pool with age.
Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program
B cell specification requires the establishment of accessible transcriptional enhancers and promoters by lineage-specific transcription factors. Loughran et al. show that Mbd3/NuRD chromatin remodeling restricts the accessibility of these regions and therefore controls B versus T cell lineage fate by preventing B cell programming transcription factors from prematurely enacting lineage commitment.
Gerner et al. show that spatial compartmentalization in lymph nodes of DCs specialized for MHC I versus MHC II presentation determines the amount of antigen these cells capture after immunization and regulates the relative generation of CD4+ versus CD8+ T cell responses.
Ucar et al. describe a novel chromatin accessibility signature of aging that is borne by memory CD8+ T cells but is detectable from PBMCs. This signature harbors the IL7R gene as a potential biomarker of aging-associated immunodeficiency.