Project funded by the National Science Centre (NCN) under the “SONATA BIS 4” call
Total project value: PLN 1,997,904.00
Total funding: PLN 1,340,184.00
Project implementation period: 01/07/2015 – 30/06/2020
Principal Investigator: Dr. Grzegorz Chodaczek
Project consortium:
Wrocław Research Centre EIT+ Ltd. – Consortium Leader
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
The aim of the project is to analyze the mechanisms of immune control in the reproductive mucosa, with particular emphasis on the activity of lymphocytes expressing the γδ T-cell receptor (γδ TCR). The study employs innovative imaging techniques based on high-resolution confocal microscopy and in vivo intravital microscopy. To achieve a comprehensive characterization of immune surveillance—essential for maintaining epithelial homeostasis during infection or injury—the proposed in situ cross-sectional analysis will be complemented with additional advanced ex vivo techniques.
Among the many cell types involved in mucosal surveillance, γδ T cells play a particularly important role. The prevailing view in epithelial immunology is that γδ T lymphocytes regulate tissue homeostasis only after recognizing self-antigens that become exposed upon injury or infection.
However, our previous studies—using a novel combination of intravital confocal microscopy and immunofluorescence techniques (Chodaczek et al., Nature Immunology 2012)—demonstrated that skin-resident γδ T cells remain in a continuously activated state due to constitutive phosphorylation of the γδ TCR, which physically immobilizes them within the epidermis.
Contrary to the widely accepted hypothesis, this suggests the continuous expression of specific antigens in healthy tissue. It remains unknown whether similar mechanisms apply to other epithelia also populated by γδ T cells. In the case of the reproductive mucosa, its immune regulation is poorly characterized despite many years of intensive research on immune responses to HIV infection.
The proposed project aims to fill this knowledge gap by:
determining the activation status of mucosal T lymphocytes,
assessing their impact on epithelial function and the induction of immune responses, and
visualizing the dynamics of cellular processes in real time, including cell motility and intercellular interactions.
