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Dr Martin A. Ivarsson

Research Interests

The research topic of the Moffett lab where I work is the maternal uterine immune system and its role in regulating the process of placentation. Specifically, how does the dominant population of uterine leukocytes, uterine Natural Killer (uNK) cells recognise MHC Class I ligands (HLA-C, E and G) on foetal trophoblast cells, and how might this affect implantation and ultimately pregnancy outcome.

My part of this research is focused on studying the phenotype and function of uNK cells using multicolour flow cytometry. I combine antibodies against numerous KIRs (the uNK cell receptors binding HLA-C) and other receptors (up to 16). This allows me to identify  subsets of uNK cells co-expressing combinations of KIRs and other receptors. I can then stimulate or co-culture uNK cells with other cells, and study the effects on the different subsets. Ultimately I hope to dissect the cellular and molecular mechanisms that govern uNK cell phenotype, differentiation and function, which in turn will feed into our group’s overall ambition to understand the inner workings of human placentation.
 

Keywords

cellular immunology ; decidua ; alloimmunity ; MHC class I ; KIR ; NK cells ; human studies ; natural killer cells ; pregnancy ; FACS ; HLA

Topics

  • reproductive immunology
  • immunology

Key Publications

1. Ivarsson, M.A. Stiglund, S., Marquart, N., Westgren, M., Gidlöf, S., and Björkström N.K. Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood. Mucosal Immunology. Jun 8. doi: 10.1038/mi.2016.50. [Epub ahead of print] (2016). 

2. Sharkey, A.M., Xiong, S., Kennedy, P.R., Gardner, L., Farrell, L. E., Chazara, O., Ivarsson, M.A., Hiby, S.E., Colucci, F., and Moffett A. Tissue-specific education of decidual NK cells. Journal of Immunology. Vol. Oct 1;195(7):3026-32 (2015). 

3. Ivarsson, M.A., Michaëlsson, J., and Fauriat, C. Activating killer cell Ig-like receptors in health and disease. Frontiers in Immunology. Vol. Apr 22;5:184 (2014).

4. Ivarsson, M.A., Loh, L., Marquardt, N., Kekäläinen, E., Berglin, L., Björkström, N.K., Westgren, M., Nixon, D.F., and Michaëlsson, J. Differentiation and functional regulation of human fetal NK cells. Journal of Clinical Investigation. Vol. Sep;123(9):3889-901 (2013).

5. Fauriat, C., Ivarsson, M.A., Ljunggren, H.-G., Malmberg, K.-J., and Michaëlsson, J. Education of human natural killer cells by activating killer cell immunoglobulin-like receptors. Blood. Vol. Feb 11;115(6):1166-74 (2010).

Other Publications

1. Marquardt, N., Kekäläinen, E., Chen, P., Kvedaraite, E., Wilson, J.N., Ivarsson, M.A., Mjösberg, J., Berglin, L., Säfholm, J., Manson, M.J., Adner, M., Al-Ameri, M., Bergman, P., Orre, A-C., Svensson, M., Dahlén, B. Dahlén, S-E., Ljunggren, H-G., and Michaëlsson, J. Human lung NK cells are predominantly comprised of highly differentiated hypofunctional CD69CD56dim cells. Journal of Allergy and Clinical Immunology In press (2016). 

2. Marquardt, N., Ivarsson, M.A., Sundström, E., Åkesson, E., Martini, E., Eidsmo, L., Mjösberg, J, Friberg, D., Kublickas, M., Ek, S., Tegerstedt, G., Seiger, Å., Westgren, M., and Michaëlsson, J.  Fetal CD103+ IL-17-producing ILC3s represent the dominant lymphocyte subset in human amniotic fluid. Journal of Immunology In Press (2016).

3. Marquardt, N., Ivarsson, M.A., Blom, K., Gonzalez, V.D., Braun, M., Falconer, K., Gustafsson, R., Fogdell-Hahn, A., Sandberg, J.K., and Michaëlsson, J. The human NK cell response to yellow fever virus 17D is primarily governed by NK cell differentiation independently of NK cell education. Journal of Immunology. Vol. Oct 1;195(7):3262-72 (2015).

4. Marquart, N. Béziat, V. Nyström, S. Hengst, J. Ivarsson, M.A., Kekäläinen, E. Johansson, H. Mjösberg, J. Westgren, M. Lankish, T.O., Wedemeyer, H. Ellis, E.C, Ljunggren H.-G. Michaëlsson, J. and Björkström N.K. Cutting Edge: Identification and characterization of human intrahepatic CD49aNK cells. Journal of Immunology. Vol. Mar 15;194(6):2467-71 (2015).

5. Buggert, M., Tauriainen, J., Yamamoto, T., Frederiksen, J., Ivarsson, M.A., Michaëlsson, J., Lund, O., Hejdeman, B., Jansson, M., Sönnerborg, A., Koup, R. Betts, M.R. and Karlsson, A.C. T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection. PLoS Pathogens. Vol. Jul 17;10(7):e100451 (2014).

6. Béziat, V., Traherne, J., Malmberg, J.-A., Ivarsson, M.A., Björkström, N.K., Retière, C., Ljunggren, H.-G., Michaëlsson, J., Trowsdale, J., and Malmberg, K.-J. Tracing dynamic expansion of human NK-cell subsets by high-resolution analysis of KIR repertoires and cellular differentiation. European Journal of Immunology. Vol. Jul;44(7):2192-6 (2014).

7. Loh, L., Ivarsson, M.A., Michaelsson, J., Sandberg, J.K., and Nixon, D.F. Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine. Mucosal Immunology. Vol. Sep l;7(5):1233-43 (2014).

8. Blom, K., Braun, M., Ivarsson, M.A., Gonzalez, V.D., Falconer, K., Moll, M., Ljunggren, H.-G., Michaëlsson, J., and Sandberg, J.K. Temporal dynamics of the primary human t cell response to yellow fever virus 17d as it matures from an effector- to a memory-type response. Journal of Immunology. Vol. Mar 1;190(5):2150-8 (2013).

9. Béziat, V., Liu, L.L., Malmberg, J.-A., Ivarsson, M.A., Sohlberg, E., Björklund, A.T., Retière, C., Sverremark-Ekström, E., Traherne, J., Ljungman, P., Schaffer M., Price, D.A., Trowsdale, Michaëlsson, J., Ljunggren, H.-G., and Malmberg, K.-J.  NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood. Vol. Apr 4;121(14):2678-88 (2013).

10. Dahlin, J.S., Ivarsson, M.A., Heyman, B., and Hallgren, J. IgE immune complexes stimulate an increase in lung mast cell progenitors in a mouse model of allergic airway inflammation PLoS One. Vol. 2011;6(5):e20261 (2011).

11. Björkström, N.K., Riese, P., Heuts, F., Andersson, S., Fauriat, C., Ivarsson, M.A., Björklund, A.T., Flodström-Tullberg, M., Michaëlsson, J., Rottenberg, M.E., Guzman, C.-A., Ljunggren, H.-G., and Malmberg, K.-J. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK cell differentiation uncoupled from NK cell education. Blood. Vol. Nov 11;116(19):3853-64 (2010).