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Identifier

000412849

Title

Impaired mitophagy in T regulatory cells is involved in breakdown of self-tolerance and development of autoimmune responses

Alternative Title

Βλάβη στο μηχανισμό της μιτοφαγίας των Τ ρυθμιστικών λεμφοκυττάρων ,συμβάλλει στην εκδήλωση αυτοάνοσων αντιδράσεων

Author

Καλαφάτη, Λυδία

Thesis advisor

Βεργίνης, Παναγιώτης

Reviewer

Σιδηρόπουλος, Πρόδρομος
Μερτσιάς, Γεώργιος

Abstract

Regulatory T cells (Tregs) play a major role in the maintenance of immune homeostasis and in the suppression of autoimmune responses. Breakdown of immune tolerance, a hallmark of autoimmune diseases, has been linked to both altered generation and impaired function of Tregs. However, the mechanism that leads to this defect remains elusive. Mitochondria are indispensable for proper function of the cell and clearance of damaged mitochondria through operation of mitophagy is essential for the survival of the cell. However, whether this mechanism is functional in Tregs during an autoimmune response has not been demonstrated. Thus our hypothesis is that impaired mitophagy in Tregs could affect their suppressive capacity and lead to development of autoimmune disorders. Herein we show that although Tregs isolated from draining lymph nodes of Mog35-55/CFA immunized mice exerted increased OXPHOS, were unable to produce ATP and accumulated damaged mitochondria compared to naïve Tregs. In addition, Tregs from immunized animals exhibited decreased mitochondrial membrane potential, enhanced production of mitochondrial ROS and impaired autophagy/mitophagy compared to naïve mice. Finally, Tregs deficient in autophagy demonstrated elevated numbers of mitochondria, increased production of mitochondrial ROS and lysosomal function. Overall, our results indicate an impaired mitophagy in Tregs during an autoimmune response that results in accumulation of dysfunctional mitochondria that might contribute to loss of Treg suppressive function. Future experiments will be focused on understanding the molecular mechanism underlying the deregulated mitophagy in Tregs in autoimmune disorders that will orientate us in new potential therapeutic targets.

Language

English

Subject

Metabolism

Mitochondria

Μεταβολισμός

Μιτοχόνδριο

Issue date

2017-12-12

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses

Views

549

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