Newest Articles
Endothelial cell fitness dictates the source of regenerating liver vasculatureEmploying a broad array of genetic lineage–tracing protocols including parabiotic pairs, Singhal et al. reveal that the fitness of liver endothelial cells (ECs) determines whether resident ECs or bone marrow–derived mononuclear cells will be adopted for vascular regeneration.
Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiencyWe report a child with inherited, complete IRF9 deficiency who suffered from life-threatening influenza pneumonitis. IRF9 deficiency disrupts the activation of ISGF3 and impairs but does not abolish cellular responses to type I IFNs, as some ISGs are induced.
High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumorsCD8+ T cells infiltrating tumors are largely dysfunctional. Brummelman and Mazza et al. identify partially exhausted CXCR5+ TIM-3– CD8+ T cells with enhanced stem-like properties and cytotoxicity infiltrating human solid tumors. These cells express candidate immunotherapeutic targets (PD-1, TIGIT and CD27) for their reinvigoration.
Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responsesB cell–intrinsic expression of activated PIK3CD (aPIK3CD) restricts immature BM B cell development while promoting the expansion of MZ and B1a B cells via enhanced survival. aPIK3CD is counter-productive during both T cell–independent and –dependent responses, limiting antigen-specific antibodies and class-switch recombination.
Sox12 promotes T reg differentiation in the periphery during colitisTanaka et al. show that Sox12, a member of SoxC family, is induced by TCR-NFAT signaling in T cells, binds to the Foxp3 promoter and drives its transcription, and induces the differentiation of T reg cells in the periphery during colitis.
One-step generation of monoclonal B cell receptor mice capable of isotype switching and somatic hypermutationJacobsen et al. describe a method to quickly generate mice carrying monoclonal immunoglobulins using CRISPR–Cas9-based genome editing in zygotes. Both chains are targeted in tandem into the Igh locus, allowing for isotype switching, somatic hypermutation, and affinity maturation.
Zebrafish blastomere screen identifies retinoic acid suppression of MYB in adenoid cystic carcinomaAdenoid cystic carcinoma (ACC) is a salivary gland malignancy that has no effective therapy and is caused by translocations involving MYB. A zebrafish chemical genetic screen identifies the retinoic acid class of compounds as potential MYB-inhibitory agents. Preclinical ACC mouse xenotransplantation models confirm the in vivo efficacy of retinoic acid, which represents a potential therapy for ACC.
Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunitySpontaneous CLIP dissociation from an autoimmunity-associated MHC II protein enhances presentation of peptides released by insulin-producing β cells. Presentation of such extracellular peptides does not require endosomal antigen processing and augments islet infiltration by CD4 T cells.
Pumping blood with self-reliance and cooperationIn this issue of JEM, Singhal et al. explore the cellular mechanisms involved in endothelial cell regeneration in the liver. Using a combination of myeloablative and nonmyeloablative approaches, the authors found that repair of the endothelium is mediated by endothelial cells themselves, but when injured, endothelial cells enlist myeloid counterparts that aid in vascular repair.
Macrophages of distinct origins contribute to tumor development in the lungLoyher et al. demonstrate that lung tumors are densely colonized by macrophages of various ontogenies. These distinct developmental origins dictate tumor-associated macrophages relative anatomical distributions, functions and responses to anti-cancer therapies.