[Frontiers in Bioscience E1, 288-298, June 1, 2009]

Immunomodulatory effects of chemokines during the early implantation window

Laura Fraccaroli1, Julio Alfieri1, Claudia Perez Leiros1, Rosanna Ramhorst1,2

1Immunopharmacology Laboratory, School of Exact and Natural Sciences, Int. Guiraldes 2160, Ciudad Universitaria, Pabellon 2 Piso 4, (C1428EHA) University of Buenos Aires, Argentina, 2Immunogenetics Laboratory, School of Medicine, Av. Cordoba 2351. University of Buenos Aires, Argentina

TABLE OF CONTENTS

1. Abstract
2. Immunomodulators of the feto-maternal cross-talk
3. Pro-inflammatory mediators in the peri-implantation window
4. Chemokines: do they contribute to a pro-inflammatory or a tolerogenic response?
5. Could RANTES be a physiological factor that contributes to feto-maternal tolerance allowing fetal survival?
5.1. RANTES as a novel immunomodulator of the maternal allogeneic response
5.2. Induction of maternal tolerance to fetal alloantigens by RANTES production in endometrial T lymphocytes.
5.3. RANTES produced by trophoblast-maternal leukocyte dialogue modulates maternal T cell response inducing a tolerance to fetal antigens
6. Chemokine network in the feto-maternal dialogue
7. Summary and Perspective
8. Acknowledgements
9. References

1. ABSTRACT

Successful implantation requires a functionally normal embryo at the blastocyst stage and a receptive endometrium as well as adequate communication between them throughout the implantation process. This cross-talk is highly regulated by a number of different kinds of molecules. Particularly, chemokines---small polypeptides that attract specific leukocyte subsets by binding to cell-surface receptors--- are also required to maintain immune-privileged sites as the feto-maternal interface. Chemokines expression involves an interdependent network with the absence of a single chemokine affecting the expression of multiple other chemokines, we have chosen to focus on just two representative examples: RANTES (regulated on normal T cell expressed and secreted) and MCP-1 (Monocyte chemo-attractant protein). Here, we present updated information on their expression levels and regulation on three different levels: 1) systemic effects on maternal allogeneic response; 2) local effects on endometrial cells; and 3) during an early stage of the feto-maternal dialogue. For each of the three levels, we analyzed data from both fertile women and patients having experienced recurrent spontaneous abortions as representative of physiological and pathological situations respectively.