Subscribe: International Immunology - Advance Access
Added By: Feedage Forager Feedage Grade B rated
Language: English
acid sensing  activation sensing  activation  cells  derived  ligand  ptregs  regulatory cells  required  sensing tlrs  sensing  tlr  tlrs  tregs 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: International Immunology - Advance Access

International Immunology Advance Access

Published: Wed, 14 Feb 2018 00:00:00 GMT

Last Build Date: Wed, 14 Feb 2018 03:48:50 GMT


Mechanisms controlling nucleic-acid-sensing Toll-like receptors

Wed, 14 Feb 2018 00:00:00 GMT

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization. Trafficking of ligand-activated TLRs in endosomal and lysosomal compartments is requisite for production of type I interferons. Activation of NA-sensing TLRs is required for the control of viruses such as herpes simplex virus and endogenous retroviruses. On the other hand, excessive activation of NA-sensing TLRs drives disease progression in a variety of inflammatory diseases including systemic lupus erythematosus, heart failure, arthritis and nonalcoholic steatohepatitis. NA-sensing TLRs are targets for therapeutic intervention in these diseases. We here focus on our recent progresses in our understanding of NA-sensing TLRs.

CD28 co-stimulation is dispensable for the steady state homeostasis of intestinal regulatory T cells

Wed, 07 Feb 2018 00:00:00 GMT

It is well-established that CD28 co-stimulation is required for the development and the proliferation of thymus-derived regulatory T cells (tTregs). Meanwhile, the role of CD28 co-stimulation in the homeostasis of peripherally-derived Tregs (pTregs) remains unclear. To clarify this issue, we analyzed Tregs in small and large intestines (SI and LI), the principle sites of pTreg development. Interestingly, and different from in the thymus, Tregs were abundant in the intestines of CD28-/- mice, and most of them were phenotypically pTregs. We showed that CD28-/- naïve T cells differentiated into pTreg in the LI after oral exposure to antigens and that CD28-/- pTregs in the LI had the same highly proliferative activity as CD28+/- cells. CD28-/- pTregs acquired these Treg-specific features at transcriptional and epigenetics levels. On the other hand, some immune suppressive molecules were downregulated in CD28-/- pTregs. Correspondingly, the suppressive activity of CD28-/- pTregs was weaker than CD28+/+ cells. These results indicate that the homeostasis of pTregs in the intestines is maintained even in the absence of CD28, whereas CD28 is required for the maximal suppressive activity of intestinal pTregs.