Development, regulation and function of human innate lymphoid cells throughout life – Jakob Michaëlsson group

The overall focus of our research is to investigate the differentiation, function and regulation of human innate lymphoid cells and T cells from fetal development to adults. We have a particularly strong focus on human NK cells in tissues in health and disease, with the long-term goal to exploit our knowledge in developing new therapies in cancer. We continuously develop new techniques for advanced analysis of immune cells, and strive to be leading in flow cytometry analysis of human NK cells.

The group is part of the Center for Infectious Medicine (CIM).

Our research

To achieve the long-term goal of our research, it's important for us to understand how human Natural Killer (NK) cells and CD8 T cells develop and function during different stages of life and during different conditions. The aim with our research is to aid in the development of new therapies in infectious diseases, cancer and transplantation.

We continuously develop new techniques for advanced analysis of immune cells, and strive to be leading in flow cytometry analysis of human NK cells and T cells (currently 29-colour flow cytometry).

Development of human innate lymphoid cells in fetal tissues

Little is known about how and where human immune cells develop and mature, and what signals are regulating innate lymphoid cell (ILC) development, including NK cells. We have previously investigated the development and function of fetal NK cells and T cells in the developing fetus, demonstrating that they are phenotypically and functionally distinct from those in adults. Within this project we are currently aiming at elucidating the developmental trajectories of human fetal ILCs from precursor stages to mature cells, and to investigate how fetal ILCs compare to adult ILCs in various human tissues.

We believe that this project will provide important knowledge regarding the development of the human immune system, which could have implications in for example in utero therapies and for our understanding of immune responses in new born babies.

Tissue-resident NK cells in the human lung and lung tumors

Most of our knowledge regarding human NK cell biology is based on studies of these cells in peripheral blood. Recently it has becoming increasingly clear that NK cells in tissues differ from those in tissues, with distinct phenotypes, function and possibly developmental origins. In this project we focus on the biology of tissue-resident NK cells in the human lung and what role they might play lung tumors. The project is a collaboration with 

Team Marquardt at The Center for Hematology and Regenerative Medicine (HERM) in Neo.

Formation of the human memory CD8+ T cell repertoire at the clonal level

CD8+ T cells play an important role in our defense against viral infections and tumors. It is well known that antigen-specific CD8+ T cells expand in viral infections and eventually form a broad repertoire of memory CD8+ T cells that can help in protecting against subsequent infections with the same virus. In this project we collaborate with Dr Jeff Mold and the Frisén lab to investigate how the repertoire of memory CD8+ T cells is shaped by distinct clonal identities over time in response to vaccination against Yellow Fever virus.

Keywords

NK cells, ILCs, CD8 T cells, development, differentiation, cancerCurrent projects

Publications

Selected publications

Complete list of publications

For a complete list of publications from Jakob Michaëlsson visit PubMed and Google scholar

Funding

We are grateful for our support from:

  • Karolinska Institutet
  • The Swedish Research Council
  • Swedish Cancer Society
  • Center for Innovative Medicine (CIMED)
  • Swedish Heart-Lung Foundation