Cytokines Regulating Trophoblast Invasion
Issue title: Maternal-fetal immune interactions
Article type: Research Article
Authors: Fitzgerald, Justine S. | Abad, Cilia | Alvarez, Angela M. | Mehta, Ratnesh Bhai | Chaiwangyen, Wittaya | Dubinsky, Valeria | Silva, Barbara Gueuvoghlanian | Gutierrez, Gabriela | Hofmann, Simone | Hölters, Sebastian | Joukadar, Jennifer | Junovich, Gisela | Kuhn, Christina | Morales-Prieto, Diana M. | Nevers, Tania | Ospina-Prieto, Stephanie | Pastuschek, Jana | Pereira De Sousa, F. Lazaro | San Martin, Sebastian; | Suman, Pankaj | Weber, Maja | Markert, Udo R.
Affiliations: Placenta-Lab, Department of Obstetrics, University Hospital of Jena, Bachstrasse, Jena, Germany | Labotarorio de Bioenergética Celular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela | Reproduction Group, School of Medicine – University of Antioquia. Medellín, Colombia | Unit for Autoimmunity and Immune Regulation, Division of Clinical Immunology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden | Halitus Instituto Médico, Marcelo T. de Alvear, Buenos Aires, Argentina | Laboratório de Obstetrícia Fisiológica e Experimental - Unifesp, Sao Paulo, Brazil | Ludwig Maximilians University of Munich, Department of Obstetrics and Gynaecology, Maistrasse, Munich, Germany | Women and Infants' Hospital and Warren Alpert Medical School of Brown University Providence, RI, USA | Biomedical Research Centre, School of Medicine, Universidad de Valparaiso, Chile | CREAS, Regional Centre of the Study of Healthy Foods, Valparaiso, Chile | Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
Note: [] Correspondence to: Dr. Justine S. Fitzgerald, Department of Obstetrics, University Hospital of Jena, Bachstrasse 18, 07743 Jena, Germany. Tel.: +49 3641 933845; Fax: +49 3641 933764; E-mail: [email protected]; www.placenta-labor.de
Abstract: Pregnancy is personally special to every woman expecting a child, but is also interesting from the perspective of an immunologist. During a physiological pregnancy, the mother's immune system decides to tolerate and foster an incorporated, non-self, non-dangerous organism. Whether the maternal reaction stems from deciphering the foreigness or safeness of this new individual, it is the general consensus that there is a foeto-maternal, bidirectional “dialogue” occurring and that the “messages” that are “spoken” are relayed through signaling mediators, which are capable of transmitting a functional command to a target cell. Much information dedicated to this theme has been gleaned in the past decade; however, the complex nature of cytokine networks jeopardizes clarity. In this review, we touch upon a list of mediators that are vital for reproduction. These factors are divided according to their receptor family, because this elucidates the characteristic signal transducing pathway, which is expected to mediate their signal within the target cell. The target cells of interest are the trophoblast, upon which we focus for several reasons: 1. the trophoblast represent the foetal compartment while participating in foeto-maternal interplay (e.g. while invading the decidua, trophoblasts are in constant communication with uterine, maternal immunocytes, which check and contain this function), 2. trophoblasts are responsible for foetal well-being (e.g. nutrition, protection from the environment) and 3. dysfunctional trophoblast function results in several pregnancy complications (e.g. preeclampsia, intrauterine growth retardation, miscarriage, preterm delivery). We summarize what is described in the literature on how these mediators are distributed within the reproductive tract, which cells are expressing their respective receptors (especially which trophoblast subsets) and how they modify trophoblast function (namely invasion, proliferation, differentiation and apoptosis). Furthermore, we unearth for which mediator the signal transducing pathway is verifiably used in trophoblast (ic) cells. Finally, we correlate actual biological importance of the mediator for reproduction by comparing murine knockout phenotypes and known positive and negative associations of these mediators with human pregnancy pathologies (as listed above). We expect this concise review to be useful to both basic researchers and clinicians who wish to obtain an overview of the reproductive cytokine network in respect to the trophoblast.
Keywords: Placenta, pregnancy, trophoblast, cytokines, cytokine receptors, chemokine receptors, immunoregulation
DOI: 10.3233/NIB-2011-023
Journal: Advances in Neuroimmune Biology, vol. 2, no. 1-2, pp. 61-97, 2011
