October 2013 | Volume 210, No. 11
- Molecular analysis of transplant rejection: marching onward
Lakkis and Billiar discuss recent advances in transcriptional profiling and how they have improved the diagnosis, prediction, and treatment of graft rejection after transplantation.
Brief Definitive Reports
- Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells
Exit of mature pDCs from the bone marrow requires the transcription factor Runx2, in part via Runx2-driven expression of CCR5.
- Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
Calcitonin gene–related peptide (CGRP) restricts HIV-1 transfer from Langerhans cells to T cells by decreasing integrin expression and increasing langerin to limit cellular conjugation.
- The PSGL-1–L-selectin signaling complex regulates neutrophil adhesion under flow
A subset of PSGL-1 is constitutively associated with L-selectin and signals through Src family kinases to activate LFA-1, which regulates neutrophil slow rolling and recruitment.
- BET bromodomain inhibition suppresses TH17-mediated pathology
The BET family of chromatin adaptors promotes TH17 differentiation, and inhibition of BET proteins protects against autoimmune diseases, including collagen-induced arthritis and EAE, in mice.
- Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function
Loss of transcription factor Bach2 results in a pulmonary alveolar proteinosis-like accumulation of surfactant proteins in the lungs due to altered function of alveolar macrophages.
- A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation
A set of 11 genes, termed the common rejection module, predicts acute graft rejection in solid organ transplant patients and may help to identify novel drug targets in transplantation.
- Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy
Aging strongly promotes inflammation responses, which may predispose individuals after cancer therapies to lethal system toxicities and pathology that can be partially prevented by TNF blockade.
- Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance
Cross talk between Wnt and IFN signaling determines the development of CML-leukemia–initiating cells and represents a mechanism for the acquisition of resistance to Imatinib at later stages of CML.
- Down-regulation of PLCγ2–β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer
Down-regulation of PLCγ2 and β-catenin signaling in tumor associated myeloid cells allows for their expansion and tumor growth in mice and humans.
- Genetic lesions associated with chronic lymphocytic leukemia transformation to Richter syndrome
Characterization of the pattern of clonal evolution from CLL to RS, the genetic determinants of CLL transformation to RS, and the pathogenetic relationship between RS and classical non–CLL-associated de novo DLBCL.
- Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia
Aberrant ZNF423 inhibits EBF-1 target genes, leads to a B cell maturation arrest in vivo, and is associated with poor outcome of ETV6-RUNX1 negative ALL.
- Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells
Generation of antigen-loaded MR1 tetramers that specifically stain MAIT cells identifies heterogeneity in phenotypes and TCR repertoires in humans and mice.
- Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
The CXCR4 antagonist plerixafor augments frequency of circulating neutrophils via release from the lung and prevents neutrophil homing to the bone marrow.
- Pten loss in the bone marrow leads to G-CSF–mediated HSC mobilization
Loss of the phosphatase and tumor suppressor gene PTEN induces G-CSF production in myeloid and stromal cells, thereby promoting HSCs mobilization from the bone marrow to the spleen and the initiation of lethal leukemia.
- Notchless-dependent ribosome synthesis is required for the maintenance of adult hematopoietic stem cells
Conditional deletion of Notchless leads to rapid deletion and exhaustion of HSCs and early progenitor cells, whereas committed progenitor cells survive as a result of differences in ribosomal biogenesis.
- Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex–mediated acute lupus glomerulonephritis
The mechanisms regulating acute and chronic glomerulonephritis are dependent on different genetic mechanisms, where the Cgnz1 allele confers kidney protection in immune complex–mediated proliferative lupus nephritis.
- Pathogenic CD4+ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes
A diabetogenic, insulin-reactive TCR transgenic mouse shows that CD4+ T cells that escape negative selection are directly recruited to islets, bypassing initial priming in pancreatic LNs, and also induce antiinsulin antibodies.
- Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse
The assembly of signaling nanoterritories at the T cell immunological synapse is controlled by the coordinated trafficking and fusion of specific vesicles containing the signaling molecules Lck, LAT, and TCRζ.
- Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy
Transient ablation of regulatory T cells in a murine model of breast carcinogenesis inhibits primary tumor and lung metastatic growth and enhances the therapeutic effect of radiotherapy, but not immune checkpoint blockade.
- RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA
Receptor for advanced glycation end-products (RAGE) detects nucleic acids and promotes DNA uptake into endosomes, which in turn lowers the immune recognition threshold for TLR9 activation.
- Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes
NOD2 signaling maintains intestinal intraepithelial lymphocytes via recognition of gut microbiota and IL-15 production.
- IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1
IL-4 and CSF-1 both contribute to macrophage proliferation during nematode infection, but IL-4 permits increased tissue macrophage density without the coincident monocyte infiltration associated with elevated CSF-1 levels.