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

Jakob Michaëlsson was recruited to CIM as a Principal Investigator in 2005, after two years as a postdoc at the Gladstone Institute of Virology and Immunology, University of California San Francisco. He received his PhD at the Karolinska Institutet in 2002, with Professor Klas Kärre as a Main Supervisor. Jakob has a longstanding interest in human fetal immune development and the biology of human NK cells and T cells in health and disease.

Group members

Caroline Boulouis completed her PhD at Karolinska Institutet in 2021, where she investigated the antimicrobial role of human MAIT cells. During her first postdoc, she studied the immunomodulatory properties of MAIT cells.

Caroline is now focusing her work on NK cells in tissue in the context of lung cancer.

Inga Rødahl was recruited to the group in March 2020, after completing her master in biotechnology at the University of Queensland, Australia. 

Inga is focusing her PhD studies on development of human fetal ILCs.

Current projects

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 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.

Selected publications

1. Divergent clonal differentiation trajectories establish CD8+ memory T cell heterogeneity during acute viral infections in humans.
   Mold JE, Modolo L, Hård J, Zamboni M, Larsson AJM, Stenudd M, Eriksson CJ, Durif G, Ståhl PL, Borgström E, Picelli S, Reinius B, Sandberg R, Réu P, Talavera-Lopez C, Andersson B, Blom K, Sandberg JK, Picard F, Michaëlsson J, Frisén J
   Cell Rep 2021 May;35(8):109174, PMID: 34038736.
    
2. Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood.
   Brownlie D, Scharenberg M, Mold JE, Hård J, Kekäläinen E, Buggert M, Nguyen S, Wilson JN, Al-Ameri M, Ljunggren HG, Marquardt N, Michaëlsson J
   Proc Natl Acad Sci U S A 2021 Mar;118(11):PMID: 33836578
    
3. Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells.
   Marquardt N, Kekäläinen E, Chen P, Lourda M, Wilson JN, Scharenberg M, Bergman P, Al-Ameri M, Hård J, Mold JE, Ljunggren HG, Michaëlsson J
   Nat Commun 2019 Aug;10(1):3841, PMID: 31451696
    
4. Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing.
   Hård J, Al Hakim E, Kindblom M, Björklund ÅK, Sennblad B, Demirci I, Paterlini M, Reu P, Borgström E, Ståhl PL, Michaelsson J, Mold JE, Frisén J
   Genome Biol 2019 Apr;20(1):68, PMID: 30935387
    
5. Human lung natural killer cells are predominantly comprised of highly differentiated hypofunctional CD69-CD56dim cells.
   Marquardt N, Kekäläinen E, Chen P, Kvedaraite E, Wilson JN, Ivarsson MA, Mjösberg J, Berglin L, Säfholm J, Manson ML, Adner M, Al-Ameri M, Bergman P, Orre AC, Svensson M, Dahlén B, Dahlén SE, Ljunggren HG, Michaëlsson J
   J Allergy Clin Immunol 2017 Apr;139(4):1321-1330.e4, PMID: 27670241
    
6. Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.
   Reinius B, Mold JE, Ramsköld D, Deng Q, Johnsson P, Michaëlsson J, Frisén J, Sandberg R
   Nat Genet 2016 Nov;48(11):1430-1435, PMID: 27668657
    
7. Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.
   Marquardt N, Ivarsson MA, Sundström E, Åkesson E, Martini E, Eidsmo L, Mjösberg J, Friberg D, Kublickas M, Ek S, Tegerstedt G, Seiger Å, Westgren M, Michaëlsson J
   J Immunol 2016 Oct;197(8):3069-3075, PMID: 27591320
    
8. Emerging insights into natural killer cells in human peripheral tissues.
   Björkström NK, Ljunggren HG, Michaëlsson J
   Nat Rev Immunol 2016 Apr;16(5):310-20, PMID: 27121652
    
9. The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education.
   Marquardt N, Ivarsson MA, Blom K, Gonzalez VD, Braun M, Falconer K, Gustafsson R, Fogdell-Hahn A, Sandberg JK, Michaëlsson J
   J Immunol 2015 Oct;195(7):3262-72, PMID: 26283480
    
10. Differentiation and functional regulation of human fetal NK cells.
    Ivarsson MA, Loh L, Marquardt N, Kekäläinen E, Berglin L, Björkström NK, Westgren M, Nixon DF, Michaëlsson J
    J Clin Invest 2013 Sep;123(9):3889-901, PMID: 23945237

Complete list of publications

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