H2020Индивидуална стипендия2019–2021

SkinTrmDeep · Tissue Resident Memory (Trm) CD8+ T cells: Genome-wide dissection of cellular differentiation and heterogeneity

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

Период: 2019-03-01 → 2021-02-28
Финансиране от ЕС: 173 857 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Специализираните Т-клетки в кожата се изследват, за да се разбере как те разпознават и унищожават ракови или заразени с вируси клетки. Познаването на тези механизми помага за подобряване на оцеляемостта при рак и лечението на болести като псориазис и витилиго.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Tissue Resident Memory (Trm) CD8+ T cells: Genome-wide dissection of cellular differentiation and heterogeneity

The action SkinTrmDeep 794827 was carried out by the researcher Dr. Beatrice Zitti under the supervision of Prof. Bryceson at the Centre of Hematology and Regenerative Medicine (HERM) at the Karolinska Institute in Stockholm. The main focus of the project was to study the mechanisms underlying the differentiation and functionality of cytotoxic lymphocyte subsets localized in the human skin. Such cells are named tissue-resident memory (Trm) cells given their ability to provide long-term protection at barriers tissue where continuous challenges require the presence of specialized cells that patrol the environment and are able to rapidly recognize and kill virus-infected and cancer cells. Emerging evidence indicates a beneficial role of CD8+ Trm cells in human solid cancers, where their densities among tumor infiltrating lymphocytes correlates with improved patient survival. In human skin, Trm cells represent the predominant lymphocyte population and they comprise subsets devoted to different protective functions contributing to local immune protection to distinct pathogens. However, Trm cells may also be associated with different T cell-mediated pathologies upon aberrant activation contributing to disease burden in psoriasis and vitiligo. Translation of these new findings to the clinic requires further studies seeking a deeper understanding of the molecular mechanisms that support the acquisition, maintenance and functionality of different Trm subsets. Capitalizing on access to unique tissue samples, strengths on high-throughput sequencing and bioinformatics the project aimed to decipher how tissue-derived signals instruct the differentiation of Trm cells with distinct phenotypes and functional capacities. The long-term goal of the project was to elucidate how cells can be controlled in settings of aberrant activation or harnessed for immunity to infections or cancer.

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

Цел на проекта

Tissue-resident memory (Trm) cells are non-circulating T lymphocytes of non-lymphoid tissues and organs that provide localized protection at barrier surfaces such as skin, gut and lungs. In human skin, Trm cells represent the predominant lymphocyte population, comprising subsets with different cytokine profiles and cytotoxic capacity. They represent an integral part of barrier immunity, mounting tailored responses to diverse pathogens, but potentially also eliciting immune pathology. Trm cell differentiation, effector mechanisms and cellular interactions remain poorly defined. I aim to decipher cytotoxic Trm cell biology in greater depth, unravelling the epigenetic framework of phenotypically and functionally distinct CD8+ Trm populations. I will rely on state-of-the-art methodologies at the host institution. Through unique collaborations and a multidisciplinary approach encompassing advanced flow cytometry, cell sorting and high-throughput sequencing, I propose to map genome-wide chromatin accessibility in skin and gut Trm cell subsets. Identification of regulatory elements critical for cell functions coupled with analyses of transcription factor binding promise to unravel the molecular mechanisms defining Trm cell ontogeny, function and tissue-specific imprinting. Moreover, with potential application to limited patient samples, single-cell RNA sequencing of cytokine-producing cells will provide a map of Trm cell heterogeneity with unprecedented resolution. This project will illuminate the role of the microenvironment in shaping tissue-resident memory, with ultimate goals to understand Trm cell-related diseases and determine common denominators required to establish tissue residency and provide basis for generating and shaping Trm cells in future cellular immunotherapies. Being at the forefront of the research on the epigenetic differentiation processes of lymphocytes, I am determined to build a strong basis for a future career as a young independent scientist.

Оригинален текст от CORDIS (на английски).

Участници

KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция