Martin Ivarsson team – Human uterine immune cells in endometrium and pregnancy
The Martin Ivarsson team studies uterine immune cells in the endometrium and the decidua (endometrium during pregnancy). We explore the heterogeneity and function of the cells and try to understand their role for establishment and maintenance of healthy pregnancies.
The Martin Ivarsson team is part of the Niklas Björkström research group at the Center for Infectious Medicine (CIM).
About our research
Our research interest is in the dynamics, variations in phenotype and function of human uterine immune cells with a particular focus on natural killer (uNK) cells, in non-pregnant and pregnant women. These cells can be said to be misnamed since they are in fact not natural killers. Instead, more and more studies indicate they regulate the placentation (attachment of the embryo and establishment of the placenta) by interacting with placenta-derived trophoblast cells, other immune cells in the uterus, as well as with cells lining the spiral arteries of the uterus. The uNK cells increase in frequency and change phenotype during each menstrual cycle and develop further in the event of a pregnancy.
Work from us and other groups have shown that the uNK cell receptor profile (which govern the cell’s function) is highly individual and that it is recapitulated each menstrual cycle. Moreover, the uNK cell profile is distinct from that of conventional NK cells in the same woman. This indicates a tight regulation of the uNK cells, which likely has to do with an important role played by them. This role remains to be fully understood.
Clinical collaborations and tissue samples for research
We make use of several clinical collaborations to obtain relevant tissue for our research. These include decidua and placenta tissue from elective terminations, endometrium from hysterectomies, menstrual blood from healthy volunteers and from women undergoing IVF. We also study patients suffering from spontaneous unexplained bleedings during pregnancies, where we try to understand what the bleeding contains, and whether it has a link to risk for miscarriage.
Methods used in our research
Methods we use include cytometry, confocal microscopy as well as more recent RNA sequencing approaches (10x Genomics and ATAC sequencing). We also study the protein content of serum, plasma, and saliva from our patient cohorts and for thus we use ELISA or OLINK’s PEA technology. With these techniques we unravel the phenotype and function of the different cells at the fetal/maternal interphase, and then seek link this information to e.g. pregnancy outcome for patients doing IVF, or to risk for miscarriage for women presenting with vaginal bleedings early in pregnancy. The long-term aim is to help develop new diagnostic and treatment methods for reproduction medicine.
Martin received his PhD from KI in 2014 and then focused on the development of human fetal natural killer (NK) cells. He then received a Wenner-Gren postdoctoral fellowship and used this to conduct postdoctoral studies at University of Cambridge, UK. Here he developed his interest for uterine immunology and in 2017 he returned to CIM to establish this line of research. Since 2018 he is an Assistant Professor and in 2020, he was awarded a startup grant from the Swedish Research Council (Vetenskapsrådet) to further study uterine immunology.
When he is not working, he enjoys spending time with his two daughters, to go for a run and to sample new food and drinks.
Corinna earned her Master’s degree in Biomedicine at KI in 2021. Her MSC thesis project was bout the expression and function of CD96 (Tactile) on uterine NK (uNK) cells, supervised by Martin Ivarsson. As a PhD student she profiles uNK cells from patients undergoing IVF treatment and patients suffering from neutropenia which allows her to tackle questions about the outcome of pregnancies, and the role of neutrophils on uNK cells. Besides projects focusing on reproductive immunology, Corinna works on COVID-19 related projects as well. In her spare time, she likes being outside, spending time with family and friends and eating good food, especially pastries.
Ellen completed her Master’s degree at Uppsala University in 2023. As a Research Assistant, her primary role involves biobanking uterine tissue cells for several projects, as well as carrying out experimental work within the team. Outside of work, Ellen spends her time on sewing projects, exploring, and sharing food with friends.
Katharina spent two years in the team as an RA and is now conducting PhD studies at the University of Copenhagen, Denmark.
- Wenner-Gren Stiftelserna
- Åke Wibergs stiftelse
- Svenska Läkaresällskapet
- Karolinska Institutets fonder
Full list of publications available at Martin Ivarsson’s Google Scholar Profile.
Immune cell profiling of vaginal blood from patients with early pregnancy bleeding.
Guterstam YC, Acharya G, Schott K, Björkström NK, Gidlöf S, Ivarsson MA
Am J Reprod Immunol 2023 Aug;90(2):e13738
Immunsystemet och graviditet.
In: Ajne G, Blomberg M, Carlsson Y. (eds.) Obstetrik. Studentlitteratur; 2021, pp 95-104. ISBN 9789144142609. Ivarsson MA, Vinnars M.
Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy.
Strunz B, Bister J, Jönsson H, Filipovic I, Crona-Guterstam Y, Kvedaraite E, Sleiers N, Dumitrescu B, Brännström M, Lentini A, Reinius B, Cornillet M, Willinger T, Gidlöf S, Hamilton RS, Ivarsson MA, Björkström NK Sci Immunol 2021 02;6(56): PMID: 33617461
Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy.
Huhn O, Ivarsson MA, Gardner L, Hollinshead M, Stinchcombe JC, Chen P, Shreeve N, Chazara O, Farrell LE, Theorell J, Ghadially H, Parham P, Griffiths G, Horowitz A, Moffett A, Sharkey AM, Colucci F
Nat Commun 2020 01;11(1):381. PMID: 31959757
29-Color Flow Cytometry: Unraveling Human Liver NK Cell Repertoire Diversity.
Filipovic I, Sönnerborg I, Strunz B, Friberg D, Cornillet M, Hertwig L, Ivarsson MA, Björkström NK
Front Immunol 2019 ;10():2692 PMID: 31798596
Single-cell reconstruction of the early maternal-fetal interface in humans.
Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, Park JE, Stephenson E, Polański K, Goncalves A, Gardner L, Holmqvist S, Henriksson J, Zou A, Sharkey AM, Millar B, Innes B, Wood L, Wilbrey-Clark A, Payne RP, Ivarsson MA, Lisgo S, Filby A, Rowitch DH, Bulmer JN, Wright GJ, Stubbington MJT, Haniffa M, Moffett A, Teichmann SA
Nature 2018 11;563(7731):347-353 PMID: 30429548
Uterine Natural Killer (NK) Cells.
Encyclopedia of Reproduction 2nd Edition. Elsevier; 2018, pp 462-467. ISBN 9780128118993. Ivarsson MA., Mofett A.
Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood.
Ivarsson MA, Stiglund N, Marquardt N, Westgren M, Gidlöf S, Björkström NK
Mucosal Immunol 2017 03;10(2):322-331PMID: 27271316