H2020Индивидуална стипендия2018–2020

DevoSignGammaDelta · Tracking γδ T cell development and TCRγδ proximal signalling

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-09-01 → 2020-08-31
Финансиране от ЕС: 160 636 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Гамма-делта Т-клетките и начинът, по който се развиват и сигнализират в тимуса, са в центъра на анализа. Разбирането им помага за подобряване на имунотерапията при рак, тъй като тези клетки могат да унищожават туморни клетки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Tracking γδ T cell development and TCRγδ proximal signalling

What is the problem/issue being addressed? T cells and B cells, the two main components of adaptive immunity, express highly diverse antigen receptors generated by somatic gene rearrangement during their development. T cell development is restricted to the specialized environment of the thymus. Two types of T cells are conserved throughout evolution and across species: alphabeta and gammadelta T cells. In the thymus, alphabeta T cells develop through discrete steps from co-receptor CD4-CD8- (double negative, DN) T-cell receptor (TCR)- via CD4+CD8+ thymocytes into mature CD4+ or CD8+ single positive TCRalphabeta+ T cells, which populate the peripheral lymphoid tissues and are restricted to recognize antigens as peptides bound to major histocompartibility complex (pMHC). gammadelta T cells develop in the thymus alongside alphabeta T cells, but rearrange a distinct TCR (TCRgammadelta) that is not restricted by classical MHC. Successive waves of gammadelta T cells develop in the fetal and later in the adult thymus and different waves are associated with variable TCR-Vgamma segment usage, functional differentiation and localization in different tissues. Unique antigen-specificities of gammadelta T cells, their high clonal frequency and pre-activated differentiation status allows for their rapid, innate-like responses and confers them non-redundant roles in immune responses to infections and tumours. Why is it important for society? gammadelta T cells can effectively kill tumour cells and provide IFNgamma-mediated protective responses against cancer. Still, in some cases they can promote tumour growth via IL-17A production. Together with the recent advancements in T cell-based immunotherapy for cancer, gammadelta T cells are becoming an attractive tool for clinical treatments. Still, our knowledge of gammadelta T cells biology and development is rather limited and requires investigation to improve fine-tuning and manipulation for their clinical use. What are the overall objectives? This research project aims to elucidate the developmental trajectories and requirements of different gammadelta T cell subsets. To this end, we investigate i) the lineage relationship from uncommitted thymic progenitor cells to mature gammadelta T cell effector subsets producing either IL-17 (named gd17) or IFNgamma (named gdIFN), ii) the impact of TCRgammadelta signalling during thymic development and iii) the role of on candidate genes differentially expressed between gd17 and gdIFN cells and their role in gammadelta T cell subsets development.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

T cells are key constituents of our immune system. Two types of T cells are conserved evolutionary and across species: αβ and γδ T cells. While αβ T cells have been intensively studied during the last decades, our knowledge on the development and activation of γδ T cells is still limited. Recently, γδ T cells have become increasingly attractive for immunotherapy of cancer due to efficient killing of tumour cells independently of major histocompatibility complex (MHC) antigen presentation. The proposed project will elucidate how T cell receptor (TCR) signalling is initiated in γδ T cells; and how it contributes to the developmental programming of γδ T cell subsets strongly implicated in cancer immunity.In a pioneer experiment, cellular barcoding and single-cell RNA sequencing will be combined with recent γδ T cell subset markers to gain unprecedented insight into precursor-product and lineage relationships in γδ T cell development; and towards identifying its key molecular determinants. Moreover, TCRγδ signalling will be addressed in thymic subset development at protein and mRNA level by cutting-edge flow-cytometry based techniques. Results of both experimental lines will be integrated to elucidate TCRγδ signalling characteristics and their impact on subset development and functional programming of γδ T cells. The acquired knowledge will enhance our understanding of γδ T cells and allow for their manipulation and fine-tuning in clinical applications.The supervisor’s outstanding expertise in γδ T cells and their role in cancer, in synergy with the researcher’s deep experience in antigen receptor signalling, form the optimal basis for this challenging project. Moreover, the researcher strongly benefits by increasing her research technology and transferable skills in a new, stimulating scientific environment within a privileged EU network. This will enable her to move to the next career stage and to further contribute to the innovative research landscape in Europe.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES · LisboaКоординаторПортугалия