April 2015 | Volume 212, No. 4
- The interaction of anticancer therapies with tumor-associated macrophages
Mantovani and Allavena provide a comprehensive review on the effects of conventional anticancer therapies on tumor-associated macrophages.
Brief Definitive Reports
- A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury
In response to sterile liver injury, CCR2hiCX3CR1low inflammatory monocytes infiltrate the liver and form a ringlike structure around the injury site. The cells then transition into CCR2lowCX3CR1hi alternative monocytes that enter the injury site; this phenotypic transition was required for optimal repair.
- Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice
Gao et al. report that genetic or pharmacological blockade of CD95 ligand prevents infiltration of peripheral myeloid cells and thereby averts toxin-induced neurodegeneration in mice.
- Inefficient clearance of myelin debris by microglia impairs remyelinating processes
Lampron et al. use a cuprizone mouse model of demyelination/remyelination to show that in CX3CR1-deficient mice, the clearance of myelin debris by microglia is impaired, affecting the integrity of axon and myelin sheaths.
- Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Dutta et al. show that targeting VACM-1 expression in splenic macrophages impairs extramedullary hematopoiesis, thus reducing inflammation in mouse ischemic heart and atherosclerotic plaques.
- IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function
Basophils orchestrate eosinophil recruitment during IgE-dependent dermatitis by interacting with inflamed endothelium and producing IL-4. IL-4 in turn induces endothelial VCAM-1 expression, which is required for subsequent eosinophil accumulation.
- Hematopoietic stem cell quiescence and function are controlled by the CYLD–TRAF2–p38MAPK pathway
Tesio at al. identify a novel pathway controlled by the tumor suppressor and deubiquitinase cylindromatosis (CYLD), which is involved in the regulation of hematopoietic stem cell quiescence and repopulation potential.
- BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms
Crotty and colleagues define the gene targets of BCL6 in primary human follicular T helper cells, revealing its primary role as a gene repressor. BCL6 bound to some loci directly and to others by interacting with AP1 and being recruited to canonical AP1-binding sites.
- T cell lipid peroxidation induces ferroptosis and prevents immunity to infection
Matsushita et al. investigated the role of the selenoenzyme glutathione peroxidae 4 (Gpx4) in T cell responses and found that loss of Gpx4 results in an intrinsic T cell developmental defect in the periphery, which leads to a failure to expand and protect from acute viral and parasitic infection.The defects were rescued with dietary supplementation of vitamin E. The Gp4−/− T cells accumulate membrane lipid peroxides and undergo cell death by ferroptosis.
- Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a
Zhou et al. demonstrate a requirement for the Let-7–Lin28b axis regulating a shift in development between fetal liver and bone marrow B lymphocyte progenitors in the generation of B1 versus B2 B cells. Specifically, the transcription factor Arid3a, induced by Lin28b and a target of Let-7 miRNA, is sufficient to recapitulate fetal B cell development from bone marrow progenitors.
- Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm
Methot et al. identify a mechanism for cytoplasmic retention of activation-induced deaminase (AID) in cells. Interactions of AID with Hsp90 and eEF1A proteins, both of which stabilize AID, promote sequential folding and retention of functional AID in the cytoplasm. Inhibition of the translation elongation factor eEF1A blocks its interaction with AID, which then accumulates in the nucleus, increasing class switch recombination and the generation of chromosomal translocation byproducts.