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Tissue innate immunity in the womb and reproduction

Tissue innate immunity in the womb and reproduction

 

Supervisor: Francesco Colucci

Co-supervisors: Francesca Gaccioli and Irving Aye

 

Mammalian reproduction depends on cyclic tissue remodelling in the womb. By destroying and repairing, innate immunity remodels tissues and is then intimately connected with tissue homeostasis.  Our research in Cambridge has shown that uterine innate lymphocytes, including natural killer cells, facilitate uterine vascular adaptations to pregnancy, promoting formation of the placenta and fetal growth (reviewed in 1).

 

Powerful immune cells and pathways have multiple regulatory checkpoints (2). Cytokines, for example, are soluble mediators of diverse immune responses with different, sometimes opposite outcome. For example, type-1 and -2 immunity are broadly pro- and anti-inflammatory. How the balance between inflammation and repair impacts on uterine adaptations to pregnancy, feto-placental growth and, ultimately, childbirth, is unclear.

 

Based on our unpublished new research, the working hypothesis of this project is that specific members of the interleukin-1 (IL-1) family of cytokines act on innate lymphocytes and impact on pregnancy outcome. We now have preliminary evidence from a prospective cohort, the Pregnancy Outcome Prediction study (3), that dysregulation of these cytokines is associated with pregnancy disorders. The aim of this project is to define the underlying mechanisms using a combination of clinical samples, transgenic preclinical models, transcriptomics, single cell cytometry, and imaging.

 

You will join the Department of Physiology, Development and Neuroscience and be based at the Department of Obstetrics and Gynaecology at the Clinical School in the Colucci team. This is an international (4) and dynamic team of talented graduate students and research associates engaged in active collaboration with several research groups within and beyond the Centre for Trophoblast Research.

 

References

 

  1. Colucci F, and Kieckbusch J. Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus. Trends in Molecular Medicine. 2015;21(2):60-67
  2. Kieckbusch J, et al. Disrupted PI3K p110d signaling dysregulates maternal immune cells and increases fetal mortality in mice. Cell Reports. 2015. 13:2817-28
  3. Sovio U, et al, Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet 2015;386(10008):2089-2097
  4. Colucci F. Imagine a world without borders: an immunologist's thoughts on Brexit. EMBO Rep. 2016;17(9):1241