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PI, Kargl

Neutrophil function in pregnancy

Pregnancy is an immunological challenge for mother and fetus, and the establishment of immune tolerance at the fetal-maternal interface is essential. The semi-allogeneic setting of trophoblast invasion and decidua development is highly regulated and accompanied by leukocyte infiltration. Innate and adaptive leukocyte accumulation and localization within the placenta is highly organized to maintain normal development. Especially the function and phenotype of macrophages has been well described (1,2). However other leukocyte populations have been identified to play a crucial role in placenta homeostasis, including neutrophils, cytotoxic and regulatory T-cells. Neutrophils form an essential part of the innate immune responses and are the first inflammatory cells migrating towards acute infections. Their role in regulating adaptive immunity is less well understood but has been described in the setting of cancer (3,4). Further, neutrophils have been implicated in the establishment of maternal tolerance through the induction of regulatory T-cells and neutrophil depletion led to abnormal development of the fetal-maternal unit in mouse models (5). Imbalance of leukocyte infiltration and localization within the placenta has been linked to complications in pregnancy, including gestational diabetes mellitus, preeclampsia and preterm labor, however a detailed picture of leukocyte dysfunction is missing.

 

 

1. Svensson-Arvelund J, Ernerudh J. (2015) The role of macrophages in promoting and maintaining homeostasis at the fetal-maternal interface. Am J Reprod Immunol, 2015; 74(2):100–109.

2. Schliefsteiner C, Peinhaupt M, Kopp S, Lögl J, Lang-Olip I, Hiden U, Heinemann A, Desoye G, Wadsack C. (2017) Human Placental Hofbauer Cells Maintain an Anti-inflammatory M2 Phenotype despite the Presence of Gestational Diabetes Mellitus. Front Immunol. doi: 10.3389/fimmu.2017.00888

3. Kargl J, Busch SE, Yang GHY, Kim KH, Hanke ML, Metz HE, Hubbard JJ, Madtes DK, McIntosh MW, Houghton AM. (2017) Neutrophils dominate the immune cell composition in non-small cell lung cancer. Nature Commun.8, 14381 doi: 10.1038/ncomms14281

4. Coffelt SB, Wellenstein MD, deVisser KE. (2016) Neutrophils in cancer: neutral no more. Nat Rev Cancer.;16(7):431-46(2016)

5. Nadkarni S, Smith J, Sferruzzi-Perri AN, Ledwozyw A, Kishore M, Haas R, Mauro C, Williams DJ, Farsky SHP, Marelli-Berg FM, Perretti M. (2016) Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy. PNAS doi:10.1073/pnas.1611944114

 

 

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