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The beneficial effects of probiotics have been described in many diseases, but the mechanism by which they modulate the immune system is poorly understood. In this study, we identified a mixture of probiotics that up-regulates CD4+Foxp3+ regulatory T cells (Tregs). Administration of the probiotics mixture induced both Tcell and B-cell hyporesponsiveness and down-regulated T helper (Th) 1,Th2, and Th17 cytokines without apoptosis induction. It also induced generation of CD4+Foxp3+ Tregs from the CD4+CD25- population and increased the suppressor activity of naturally occurring CD4+CD25- Tregs. Conversion of T cells into Foxp3+ Tregs is directly mediated by regulatory dendritic cells (rDCs) that express high levels of IL-10, TGF-β, COX-2, and indoleamine 2,3-dioxygenase. Administration of probiotics had therapeutical effects in experimental inflammatory bowel disease, atopic dermatitis, and rheumatoid arthritis. The therapeutical effect of the probiotics is associated with enrichment of CD4+Foxp3+ Tregs in the inflamed regions. Collectively, the administration of probiotics that enhance the generation of rDCs and Tregs represents an applicable treatment of inflammatory immune disorders. [ABSTRACT FROM AUTHOR]

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Primary destabilizing N-terminal residues (NdP) are recognized directly by the targeting machinery. The recognition of secondary destabilizing N-terminal residues (Nds) is preceded by conjugation of an NdP residue to Nds of a polypeptide substrate. In eukaryotes, ATE1-encoded arginyl-transferases (RD,E,C*-transferases) conjugate Arg (R), an NdP residue, to Nds residues Asp (D), Glu (E), or oxidized Cys residue (C*). Ubiquitin ligases recognize the N-terminal Arg of a substrate and target the (ubiquitylated) substrate to the proteasome. In prokaryotes such as Escherichia coil, NdP residues Leu (L) or Phe (F) are conjugated, by the aat-encoded Leu/Phe-transferase (L/FK,R-transferase), to N- terminal Arg or Lys, which are NdP in prokaryotes but NdP in eukaryotes. In prokaryotes, substrates bearing the NdP residues Leu, Phe, Trp, or Tyr are degraded by the proteasome-like CIpAP protease. Despite enzymological similarities between eukaryotic RD,E,C*-transferases and prokaryotic L/FK,R-transferases, there is no significant sequelogy (sequence similarity) between them. We identified an aminoacyl-transferase, termed Bpt, in the human pathogen Vibrio vulnificus. Although it is a sequelog of eukaryotic RD,E,C*-transferases. this prokaryotic transferase exhibits a ‘hybrid’ specificity, conjugating NdP Leu to Nds Asp or Glu. Another aminoacyl-transferase, termed ATEL1, of the eukaryotic pathogen Plasmodium falciparum, is a sequelog of prokaryotic L/FK,R-transferases (Aat), but has the specificity of eukaryotic RD,C,E*-transferases (ATE1). Phylogenetic analysis suggests that the substrate specificity of R-transferases arose by two distinct routes during the evolution of eukaryotes. [ABSTRACT FROM AUTHOR]

An abstract of the article "DNA looping-dependent autorepression of LEE1 P1 promoters by Ler in enteropathogenic Escherichia coli (EPEC)," by Abhayprasad Bhat and colleagues is presented.