cDC1s Promote Atherosclerosis via Local Immunity and Are Targetable for Therapy.

Background: Atherosclerosis is characterized by immune cell accumulation in the arterial wall and adaptive CD4 T helper 1 immunity contributes to atherosclerosis development. However, how conventional dendritic cells (DCs) orchestrate this adaptive response remains controversial. This study unveils strategies for the gain and loss of function of cDCs to decipher their role in atherosclerosis induction in relation to adaptive T-cell immunity.

C/EBPα activates expression in myeloid progenitors at the +56-kb enhancer to initiate cDC1 development.

Development of type 1 conventional dendritic cells (cDC1s) underlies the capacity to generate antiviral and antitumor immune responses. Here, we identify the basis for cDC1 development from its earliest progenitors, determining the hierarchy of several required transcription factors and uncovering a series of mandatory cis interactions between constituent enhancers within the superenhancer. We produced in vivo mutations of two C/EBPα binding sites that comprise the  +56-kilobase (kb) enhancer that markedly reduced IRF8 expression in all myeloid progenitors and impaired cDC1 development.

Layer-by-Layer Interdigitated CuS/AuS Heteronanoplates by Selectively Blocking the Pathway of Cation Exchange Reaction.

Cation exchange reactions (CERs), recognized as a promising postsynthetic modification strategy, have garnered significant interest for generating thermodynamically unfavorable structural features, such as heterointerfaces. The formation of these heterointerfaces, which exhibit physicochemical properties distinct from those of their individual components, relies on precise control over the diffusion pathways of externally introduced cations as they migrate from the surface into the crystal interior. However, achieving regiospecific modulation of cation diffusion to rationally design heterointerfaces remains a formidable challenge.

Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2.

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo.

Remnant Copper Cation-Assisted Atom Mixing in Multicomponent Nanoparticles.

Nanostructured high-/medium-entropy compounds have emerged as important catalytic materials for energy conversion technologies, but complex thermodynamic relationships involved with the element mixing enthalpy have been a considerable roadblock to the formation of stable single-phase structures. Cation exchange reactions (CERs), in particular with copper sulfide templates, have been extensively investigated for the synthesis of multicomponent heteronanoparticles with unconventional structural features. Because copper cations within the host copper sulfide templates are stoichiometrically released with incoming foreign cations in CERs to maintain the overall charge balance, the complete absence of Cu cations in the nanocrystals after initial CERs would mean that further compositional variation would not be possible by subsequent CERs.

Transcription factor C/EBPα is required for the development of Ly6C monocytes but not Ly6C monocytes.

Monocytes comprise two major subsets, Ly6C classical monocytes and Ly6C nonclassical monocytes. Notch2 signaling in Ly6C monocytes triggers transition to Ly6C monocytes, which require , , , and . By comparison, less is known about transcriptional requirements for Ly6C monocytes.

IL-6 selectively suppresses cDC1 specification via C/EBPβ.

Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively.

Mechanisms of CD40-dependent cDC1 licensing beyond costimulation.

CD40 signaling in classical type 1 dendritic cells (cDC1s) is required for CD8 T cell-mediated tumor rejection, but the underlying mechanisms are incompletely understood. Here, we identified CD40-induced genes in cDC1s, including Cd70, Tnfsf9, Ptgs2 and Bcl2l1, and examined their contributions to anti-tumor immunity. cDC1-specific inactivation of CD70 and COX-2, and global CD27 inactivation, only partially impaired tumor rejection or tumor-specific CD8 T cell expansion.

Single-cell deletion analyses show control of pro-T cell developmental speed and pathways by Tcf7, Spi1, Gata3, Bcl11a, Erg, and Bcl11b.

As early T cell precursors transition from multipotentiality to T lineage commitment, they change expression of multiple transcription factors. It is unclear whether individual transcription factors directly control choices between T cell identity and some alternative fate or whether these factors mostly affect proliferation or survival during the normal commitment process. Here, we unraveled the impacts of deleting individual transcription factors at two stages in early T cell development, using synchronized in vitro differentiation systems, single-cell RNA-seq with batch indexing, and controlled gene-disruption strategies.

The impaired redox balance in peroxisomes of catalase knockout mice accelerates nonalcoholic fatty liver disease through endoplasmic reticulum stress.

Peroxisomes are essential organelles for maintaining the homeostasis of lipids and reactive oxygen species (ROS). While oxidative stress-induced endoplasmic reticulum (ER) stress plays an important role in nonalcoholic fatty liver disease (NAFLD), the role of peroxisomes in ROS-mediated ER stress in the development of NAFLD remains elusive. We investigated whether an impaired peroxisomal redox state accelerates NAFLD by activating ER stress by inhibiting catalase, an antioxidant expressed exclusively in peroxisomes.

Transgelin-2 in immunity: Its implication in cell therapy.

Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses.