Periodic Reporting for period 2 - RESIDE (Dissecting tissue-resident lymphocyte homeostasis in humans)
Reporting period: 2022-08-01 to 2024-01-31
The human immune system is incredibly complex. We need it to combat pathogens and cancer but it can also cause damage such as acute and chronic inflammation as well as autoimmunity if it is misdirected. The immune system is present throughout the human body in all different organs. Until recently, we had the view that immune cells were continuously travelling between circulation and different organs. However, recent insights suggest that most immune cells instead permanently inhabit different organs. Yes, many details on how this is regulated remain obscure. In the current project we aim to provide ground-breaking new knowledge on how immune cell tissue-residency is formed. These insights will be crucial to understand how immune systems in different organs are formed and in the longer run what goes wrong when the immune system is failing us.
During the first half of the project, we have studied immune cells in different human organs as well as in a mouse model and through these studies been able to identify which immune cells that constitute the “tissue-resident” fraction of cells. We have further identified a number of regulatory elements (transcription factors) that we are currently exploring in more functional experiments. For the performed work we are using the latest single-cell methods which allows us to acquire in-depth data on very limited patient samples.
Our work in identifying “bona fide” human tissue resident lymphocytes represent a clear advancement beyond state of the art. Until the end of the project we expect to further solidify these findings by publishing them (refinement through review processes) as well as in the final aims of the proposal provide additional mechanistic insights into the regulation of tissue immune systems.