Type 1 diabetes is an autoimmune process predominantly T-cell mediated CD26 plays a role in T-cell costimulation, migration, memory development, thymic maturation and emigration patterns In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naive (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)) In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased The indices of intermediate- and long-term glycaemic control were associated negatively with the number of CM and N cells while positively with the number of TEMRA cells The considerable accumulation of TEMRA T cells in our patients suggests life-long stimulation by protracted antigen exposure (viruses, other agents or residual self-antigens?) or a homeostatic defect in the regulation/contraction of immune responses

Erratum: Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells (Cell Death and Differentiation (2012) 19 (1892) DOI: 10.1038/cdd.2012.116)

Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes.

Proteins destined for the secretory pathway are processed in the endoplasmic reticulum (ER) where a delicate balance exists between protein folding and degradation of terminally misfolded proteins. Different physiological as well as pathological stress conditions however, can lead to an imbalance between the ER protein folding capacity and protein load, giving rise to an accumulation of misfolded proteins in the ER lumen, a condition dubbed as ‘ER stress’. In an attempt to meet the increased folding demand, cells utilize a conserved signaling pathway, the unfolded protein response (UPR), which is initially charged to re-establish ER homeostasis and support survival. If this mechanism fails, persistent ER stress will eventually cause this cytoprotective UPR to switch into a cell death pathway that can activate mitochondrial apoptosis. As such, the dual function of the UPR in controlling cell fate may play a part in disease development and response to stress signals in conflicting ways. The lethal arm of the UPR may contribute to pathologies that are linked to unscheduled cell death, like diabetes and certain neurodegenerative diseases such as Alzheimer's and Parkinson’s, or be utilized by certain anticancer drugs to kill cancer cells. On the other hand, activation of the pro-survival function of the UPR may assist processes like tumorigenesis and chemoresistance, by endowing cancer cells with an increased capability to adapt to their hostile environment and to cope with cellular damage. Therefore, a better understanding of the different signaling pathways that emanate from the stressed ER and how their integration modulates cell fate decisions represents a crucial requirement to develop new strategies aimed at targeting the UPR for therapeutic purposes.

ER Stress Signaling Pathways in Cell Survival and Death

/pdf/erratum-anti-apoptotic-effect-of-hyperglycemia-can-allow-clp3c0hghh.pdf

Erratum: Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells (Cell Death and Differentiation (2012) 19 (1892) DOI: 10.1038/cdd.2012.116)

Citations

Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes.

ER Stress Signaling Pathways in Cell Survival and Death

Related Papers (5)

Mitochondria, Cell Death, and B Cell Tolerance

Regulation of activation-induced cell death of mature T-lymphocyte populations.

Pathways of apoptotic and non-apoptotic death in tumour cells.

Role of apoptosis in autoimmunity.

The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy: Death from inside out