Periodic Reporting for period 3 - STEP 2 (Spatiotemporal regulation of T-cell Priming)
Reporting period: 2022-09-01 to 2024-02-29
The initiation of an adaptive immune response is orchestrated in secondary lymphoid organs like lymph nodes and the spleen. Here, different cell types must come together and interact, exchange information, and activate each other in a highly coordinated manner. The task of the immune system is to rapidly induce a highly effective and specific immune response to ward off invading pathogens. The underlying problem of orchestrating a complex immune response that involves different specialized cell types is reminiscent to the challenges encountered during teamwork. Different people with different expertise must come together, find a proper way to efficiently communicate, interact and together work towards a common goal. In the past, the research focused on the essential cell types (team members) that participate in the initiation of an effective immune response against different classes of pathogens. In this proposal we aim to elucidate novel means, the specific context (microenvironment) and regulatory elements of immune cells (team member) interactions. The first aim of this project is to reveal previously unexplored means of intercellular communication. In analogy of teamwork this refers to the question how to keep all the team members focused on the common goal and additionally whether there are unexpected means of communication between team members (e.g. social media) that are important to reach the goal efficiently. The second aim of this project is to study specific microenvironments (local cytokine and other inflammatory cues) in which immune cell interactions are executed and how these environmental cues impact on the overall immune response. Finally, we would like to understand the regulatory elements and feedback mechanisms that guide or inhibit the immune response and if there are environments/ niches where these feedback mechanisms are most active. In other words, is the success of a team dependent on the environment of the team meetings, whether it’s a meeting room or a coffee bar, inside or outside the building? Are there specific regulatory elements that are active in one but not the other environment? Understanding how immune cells interact as a team to generate an effective immune response is essential if we aim to manipulate the system (therapy) to alter disease outcomes. This applies to both enhancing immune responses against acute and chronic infections or cancer, but also to dampen unwanted immune reactions in the context of autoimmunity.
Main results so far:
1.) Discovered spatio-temporal development and organization of dendritic cell network in lymph nodes. Data support a new model of development which we term conveyor belt model.
2.) Elucidated spatio-temporal regulation of Treg cell mediated control over CD8 T cell responses.
1.) Discovered spatio-temporal development and organization of dendritic cell network in lymph nodes. Data support a new model of development which we term conveyor belt model.
2.) Elucidated spatio-temporal regulation of Treg cell mediated control over CD8 T cell responses.
Expected results:
Identifying critical molecular factors that determine efferocytosis by cDC1
Elucidating the biological function of STEP2 phase of CD8 T cell activation.
Uncovering the mechanistic basis of Treg mediated control over CD8 T cells during viral infection.
Identifying critical molecular factors that determine efferocytosis by cDC1
Elucidating the biological function of STEP2 phase of CD8 T cell activation.
Uncovering the mechanistic basis of Treg mediated control over CD8 T cells during viral infection.