CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney

Dendritic cells (DCs) interface innate and adaptive immunity in nonlymphoid organs; however, the exact distribution and types of DC within the kidney are not known. We utilized CX3CR1GFP/+ mice to characterize the anatomy and phenotype of tissue-resident CX3CR1+ DCs within normal kidney. Laser-scanning confocal microscopy revealed an extensive, contiguous network of stellate-shaped CX3CR1+ DCs throughout the interstitial and mesangial spaces of the entire kidney. Intravital microscopy of the superficial cortex showed stationary interstitial CX3CR1+ DCs that continually probe the surrounding tissue environment through dendrite extensions. Flow cytometry of renal CX3CR1+ DCs showed significant coexpression of CD11c and F4/80, high major histocompatibility complex class II and FcR expression, and immature costimulatory but competent phagocytic ability indicative of tissue-resident, immature DCs ready to respond to environment cues. Thus, within the renal parenchyma, there exists little immunological privilege from the surveillance provided by renal CX3CR1+ DCs, a major constituent of the heterogeneous mononuclear phagocyte system populating normal kidney

An exploration of ebook selection behavior in academic library collections

Academic libraries have offered ebooks for some time, however little is known about how readers interact with them while making relevance decisions. In this paper we seek to address that gap by analyzing ebook transaction logs for books in a university library

Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation.

Humans and mice lacking functional caspase-8 in T cells manifest a profound immunodeficiency syndrome due to defective T cell antigen receptor (TCR)-induced NF-kappaB signaling and proliferation. It is unknown how caspase-8 is activated following T cell stimulation, and what is the caspase-8 substrate(s) that is necessary to initiate T cell cycling. We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex. Activation of caspase-8 in lipid rafts is followed by rapid cleavage of c-FLIP(L) at a known caspase-8 cleavage site. The active caspase.c-FLIP complex forms in the absence of Fas (CD95/APO1) and associates with the NF-kappaB signaling molecules RIP1, TRAF2, and TRAF6, as well as upstream NF-kappaB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to the TCR. The lack of caspase-8 results in the absence of MALT1 and Bcl-10 in the active caspase complex. Consistent with this observation, inhibition of caspase activity attenuates NF-kappaB activation. The current findings define a link among TCR, caspases, and the NF-kappaB pathway that occurs in a sequestered lipid raft environment in T cells

miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation

B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development

Variations in MHC Class II Antigen Processing and Presentation in Health and Disease

Chemical Immunolog

Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development

10.1016/S0092-8674(02)01111-XCell1115621-633CELL