KLRG1 impairs regulatory T-cell competitive fitness in the gut.

Immune homeostasis requires the tight, tissue-specific control of the different CD4 Foxp3 regulatory T (Treg) cell populations. The cadherin-binding inhibitory receptor killer cell lectin-like receptor G1 (KLRG1) is expressed by a subpopulation of Treg cells with GATA3 effector phenotype. Although such Treg cells are important for the immune balance, especially in the gut, the role of KLRG1 in Treg cells has not been assessed.

Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG1 GATA3 regulatory T cells in mice.

CD4 Foxp3 regulatory T (Treg) cells include differentiated populations of effector Treg cells characterized by the expression of specific transcription factors. Tumours, including intestinal malignancies, often present with local accumulation of Treg cells that can prevent tumour clearance, but how tumour progression leads to Treg cell accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition and tumour progression, promotes the accumulation of intestinal Treg cells by the specific accumulation of the KLRG1 GATA3 Treg subset.

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction.

CD4(+) T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3(+) regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4(+) T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4(+) T lymphocytes.

Higher Sensitivity of Foxp3+ Treg Compared to Foxp3- Conventional T Cells to TCR-Independent Signals for CD69 Induction.

T lymphocytes elicit specific responses after recognizing cognate antigen. However, antigen-experienced T cells can also respond to non-cognate stimuli, such as cytokines. CD4+ Foxp3+ regulatory T cells (Treg) exhibit an antigen-experienced-like phenotype.

Proteomic characterization of aggregating proteins after the inhibition of the ubiquitin proteasome system.

Protein aggregation, which is associated with the impairment of the ubiquitin proteasome system, is a hallmark of many neurodegenerative diseases. To better understand the contribution of proteasome inhibition in aggregation, we analyzed which proteins may potentially localize in chemically induced aggregates in human neuroblastoma tissue culture cells. We enriched for proteins in high-density structures by using a sucrose gradient in combination with stable isotope labeling with amino acids in cell culture (SILAC).

Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition.

Background: Protein aggregation is a hallmark of many neurodegenerative diseases and has been linked to the failure to degrade misfolded and damaged proteins. In the cell, aberrant proteins are degraded by the ubiquitin proteasome system that mainly targets short-lived proteins, or by the lysosomes that mostly clear long-lived and poorly soluble proteins. Both systems are interconnected and, in some instances, autophagy can redirect proteasome substrates to the lysosomes.