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Identifier

000426888

Title

Investigation of the mechanisms of anti-TIGIT antibody protective function in allergic airway disease

Alternative Title

Διερεύνηση του προστατευτικού μηχανισμού δράσης του αντι-TIGIT στην αλλεργική ασθένεια των αεραγωγών

Author

Κωστοπούλου, Ελένη

Thesis advisor

Βεργίνης, Παναγιώτης

Reviewer

Τσατσάνης, Χρήστος
Μπερτσιάς, Γεώργιος

Abstract

The increased prevalence of allergic diseases observed in western countries during the last decades has raised the concern over these disorders. The underlying etiology remains unclarified, although genetic and environmental factors, together with modern lifestyle seem responsible. Asthma is considered one of the most common forms of allergic diseases, presenting various phenotypes attributed to different molecular pathways. Thus, the design of efficient therapies targeting asthma is challenging. Albeit type 2 immune responses (Th2) were initially thought to be solely driving allergic asthma induction, recent evidence supports the involvement of non-Th2-derived factors in the pathogenesis of this disease, highlighting its complexity. Asthmatic responses are suppressed by a population of T lymphocytes, the so-called T regulatory cells (Tregs), which firmly promote immune homeostasis and tolerance induction. Breakage of tolerance against allergens due to impaired Treg cell function can result in the development of allergy and asthma. Recently, a Treg cell subset exhibiting enhanced immunosuppressive capacity associated with the expression of the TIGIT (T cell immunoglobulin and ITIM domain) receptor was identified. Interestingly, this Treg subpopulation was found to differentially affect distinct Th cell lineages, as Th1 and Th17 responses are negatively regulated, while Th2 responses are not hindered. Moreover, previous research of our lab showed that TIGIT exerts a fostering effect on Th2 responses upon allergen challenges in an OVA-induced allergic asthma model, as blockade of this molecule significantly blunted allergic responses. The question raised by this study was whether this effect was due to blockade of Th2- or/and Treg-derived TIGIT and, therefore, the objective of the present dissertation was to investigate the putative implication of TIGIT+ Tregs in anti-TIGIT-mediated attenuation of allergic airway inflammation. Results showed that TIGIT+ Tregs are dispensable for the amelioration of allergic responses upon TIGIT blockade during challenges. Further investigation is needed to elucidate the complex molecular pathways leading to TIGIT-mediated aggravation of Th2 responses in asthma. Shedding light on these underlying mechanisms in the Th2 context is of great value, since TIGIT is emerging as a promising therapeutic target not only for asthma treatment, but also for cancer immunotherapy.

Language

English

Subject

Allergic asthma

DEREG

DT-mediated Treg cell depletion

Foxp3

Regulatory T cells

Th2 responses

Th2 αποκρίσεις

Αλλεργικό άσθμα

Απαλοιφή Τ ρθθμιστικών κυττάρων με χορήγηση DT