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Fetomaternal immune cross-talk and its consequences for maternal and offspring's health

Abstract

An improved mechanistic understanding of the adaptational processes mounted during mammalian reproduction is emerging. Intricate pathways occurring at the fetomaternal interface, such as the formation of a functional synapse between invading fetal trophoblast cells, and the involvement of various maternal immune cell subsets and epigenetically modified decidual stromal cells have now been identified. These complex pathways synergistically create a tolerogenic niche in which the semiallogeneic fetus can develop. New insights into fetomaternal immune cross-talk may help us to understand the pathogenesis of pregnancy complications as well as poor postnatal health. Moreover, the effects of maternal immune adaptation to pregnancy on autoimmune disease activity are becoming increasingly evident. Thus, insights into fetomaternal immune cross-talk not only advance our understanding of pregnancy-related complications but also may be informative on how immune tolerance can be modulated in clinical settings outside the context of reproduction.

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Figure 1: Key pathways involved in immune tolerance toward the fetus during the first trimester of human pregnancy.
Figure 2: Generation and function of CD4+ Treg cells T cell receptor-expressing thymocytes can upregulate FoxP3 and differentiate into Treg cells in the thymus (tTreg cells, top).
Figure 3: Fetomaternal immune cross-talk: consequences for pregnancy maintenance and postnatal health.

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Acknowledgements

The writing of this review article was made possible by grants provided by the German Research Foundation (AR232/19), the Foundation for Research and Science Hamburg (1232/102), the Werner Otto Foundation (4/79), AllerGen NCE (09B6) and the World Health Organization (A65097) to P.C.A. and K.H.

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Arck, P., Hecher, K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med 19, 548–556 (2013). https://doi.org/10.1038/nm.3160

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