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Function and regulation of tissue resident memory T cells in the female reproductive tract: impact on maternal health during pregnancy
Like other mucosal tissues, the female reproductive tract also harbours tissue-resident memory cells, but it is unclear how these cells adapt to the profound tissue remodelling and phases of substantial inflammation in the uterus during pregnancy. We aim to unravel these pathways and propose that our insights will aid in identifying activation checkpoints that can be targeted in obstetric disorders to improve pregnancy success.
Hypothesis
Team
Prof. Dr. rer. nat.
Hans-Willi Mittrücker
Principal Investigator
Dr. rer. hum. biol.
Kristin Thiele
Principal Investigator
Íris da Mota Lima Correia Ramos
PhD Student
Twisha Kejriwal
PhD Student
Project-related publications
Thiele, K., Ahrendt, L.S., Hecher, K., and Arck, P.C. (2019). The mnemonic code of pregnancy: comparative analyses of pregnancy success and complication risk in primary and secondary human pregnancies. Journal of Reproductive Immunology.
Yüzen, D., Arck, P.C., and Thiele, K. (2022). Tissue-resident immunity in the female and male reproductive tract. Semin Immunopathol 44, 785–799. https://doi.org/10.1007/s00281-022-00934-8.
Hierweger, A.M., Engler, J.B., Friese, M.A., Reichardt, H.M., Lydon, J., DeMayo, F., Mittrücker, H.-W., and Arck, P.C. (2019). Progesterone modulates the T-cell response via glucocorticoid receptor-dependent pathways. Am J Reprod Immunol 81, e13084. https://doi.org/10.1111/aji.13084.
Thiele, K., Hierweger, A.M., Riquelme, J.I.A., Solano, M.E., Lydon, J.P., and Arck, P.C. (2019). Impaired progesterone-responsiveness of CD11c+ dendritic cells affects the generation of CD4+ regulatory T cells and is associated with intrauterine growth restriction in mice. Frontiers in Endocrinology, section Reproduction10. https://doi.org/10.3389/fendo.2019.00096.
Diao, L., Hierweger, A.M., Wieczorek, A., Arck, P.C., and Thiele, K. (2021). Disruption of Glucocorticoid Action on CD11c(+) Dendritic Cells Favors the Generation of CD4(+) Regulatory T Cells and Improves Fetal Development in Mice. Front Immunol 12, 729742. https://doi.org/10.3389/fimmu.2021.729742.
Krebs, C.F., Reimers, D., Zhao, Y., Paust, H.-J., Bartsch, P., Nuñez, S., Rosemblatt, M.V., Hellmig, M., Kilian, C., Borchers, A., … Mittrücker, H.W. (2020). Pathogen-induced tissue-resident memory T(H)17 (T(RM)17) cells amplify autoimmune kidney disease. Sci Immunol 5, eaba4163. https://doi.org/10.1126/sciimmunol. aba4163.
Yüzen, D., Urbschat, C., Schepanski, S., Thiele, K., Arck, P.C., and Mittrücker, H.-W. (2023). Pregnancyinduced transfer of pathogen-specific T cells from mother to fetus in mice. EMBO Rep 24, e56829. https://doi.org/10.15252/embr.202356829.
Bertram, T., Reimers, D., Lory, N.C., Schmidt, C., Schmid, J., C Heinig, L., Bradtke, P., Rattay, G., Zielinski, S., Hellmig, M., … Mittrücker, H.W. (2023). Kidney-resident innate-like memory γδ T cells control chronic Staphylococcus aureus infection of mice. Proc Natl Acad Sci U S A 120, e2210490120. https://doi.org/10.1073/pnas.2210490120.
Engels, G., Hierweger, A.M., Hoffmann, J., Thieme, R., Thiele, S., Bertram, S., Dreier, C., Resa-Infante, P., Jacobsen, H., Thiele, K., …Mittrücker H.W. (2017). Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice. Cell Host & Microbe 21, 321–333. https://doi.org/10.1016/j.chom.2017.02.020.