415 research outputs found
In-depth tissue profiling using multiplexed immunohistochemical consecutive staining on single slide
No full textItem does not contain fulltex
Terminal differentiation of dendritic cells
No full textDendritic cells (DCs) are essential for the initiation of an effective immune response. Despite this, our understanding of the molecular regulation of this important cell type has lagged significantly behind that of other lymphoid populations such as B and T cells, but recent development of various tools has greatly facilitated progress in the field. Here, we review the transcription factors that drive peripheral DC subset fate decisions. While Pu.1, Ikaros, and Gfi-1 are essential for precursor DCs to give rise to monocytes, conventional DCs, and plasmacytoid DCs, the balance between E2-2 and Id2 directs committed precursors along a pDC or cDC lineage, respectively. Several transcription factors such as Batf3, Nfil3, and Id2 are required for different DC subsets at steady-state and drive segregation into the individual DCs subsets late in development in the CD8 lineage. During inflammation, CD8-expressing DCs emerge that feature many of the hallmarks of classical CD8α DCs but surprisingly do not depend on the same transcription factors. Thus, the immune system has developed two pathways of DC differentiation that enable it to maintain homeostatic balance and to respond rapidly to the emergency requirement for DCs that might occur during infection
Abstract 334: PTEN-L regulates epithelial growth and macrophage function
No full textAbstract
PTEN is among the most frequently mutated and deleted tumor suppressor genes in many malignancies, including breast cancer. An alternatively translated long form of PTEN, termed PTEN-L, has divergent functionality from PTEN, although its function at the organism level has not been studied. Here, we report a knockout mouse with specific ablation of PTEN-L expression but intact expression of PTEN. These mice display mammary ductal hyperplasia characterized by increased luminal growth and increased numbers of macrophages in the surrounding stroma. Macrophages are particularly affected by PTEN-L loss, with significant changes to their secretomes and functional deficiencies in clearing bacterial infections, consistent with a shift toward an M2-like polarization. Overall, these findings demonstrate that PTEN-L has unique functions in regulating mammary epithelial growth and macrophage functionality that are independent of canonical PTEN.
Citation Format: Andrew L. Wolfe, Benjamin D. Hopkins, Sebastián A. Riquelme, Kipyegon Kitur, Sait Ozturk, Kyeongah Kang, Romain Remark, Adeeb Rahman, Chyuan-Sheng Lin, Miriam Merad, Matthias Szabolcs, Shu-Hsia Chen, Alice Prince, Ramon Parsons. PTEN-L regulates epithelial growth and macrophage function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 334. doi:10.1158/1538-7445.AM2017-334</jats:p
PU.1 Takes Control of the Dendritic Cell Lineage
No full textDespite the importance of the cytokine receptor flt3 in dendritic cell (DC) homeostasis, little is known about its regulation during DC development. In this issue of Immunity, Carotta et al. (2010) reveal that the transcription factor PU.1 controls Flt3 expression in hematopoietic progenitors in a dose-dependent manner
Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages
No full textInternational audienceThe COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19
Regulation of microglia development and homeostasis
No full textMicroglia represent the resident macrophages of the central nervous system (CNS) and account for 10% of the adult glial cell population in the normal brain. Although microglial cells are thought to contribute to most pathological conditions including CNS infections, neuroinflammatory lesions, brain tumors, and neurodegenerative diseases, their exact role in CNS development, homeostasis, and disease remains poorly understood. In contrast to most macrophage populations, microglia survive high-dose ionizing radiation and maintain themselves locally and independently of circulating precursors in the steady state. However, controversies remain on the origin of microglia in the brain and whether they could potentially be repopulated by circulating myeloid precursors after brain injury. Microglia-targeted therapies through the use of genetically modified circulating hematopoietic cells proved to be a promising therapeutic strategy for the treatment of brain diseases. It is thus of great importance to understand the contribution and developmental cues of circulating myeloid cells as potential microglia progenitors to the adult pool of microglia in the steady state and under inflammatory conditions
Publisher Correction: Innate IL-13 licenses dermal type 2 dendritic cells for efficient T helper 2 cell responses
No full text- …
