CRITICAL ROLE OF GALECTIN-1 IN FETOMATERNAL TOLERANCE

S. BLOIS; J. ILARREGUI; M. GARCIA; M. TOSCANO; G. BIANCO; G. RABINOVICH; P. ARCK

RIO DE JANEIRO

Congreso; 13TH INTERNATIONAL CONGRESS OF IMMUNOLOGY; 2007

ICI 2007

Critical role of galectin-1 in fetomaternal tolerance Author Block: S. M. Blois1, J. M. Ilarregui2, M. Garcia1, M. A. Toscano2, G. A. Bianco2, G. A. Rabinovich2, P. C. Arck1;S. M. Blois1, J. M. Ilarregui2, M. Garcia1, M. A. Toscano2, G. A. Bianco2, G. A. Rabinovich2, P. C. Arck1;2, P. C. Arck1; 1Charit¨¦, University Medicine Berlin, Berlin, Germany, 2Lab Immunogenetics, Hospital de Cl¨ªnicas, UBA, Buenos Aires, Argentina.Charit¨¦, University Medicine Berlin, Berlin, Germany, 2Lab Immunogenetics, Hospital de Cl¨ªnicas, UBA, Buenos Aires, Argentina. Abstract: Blastocyst implantation and perpetuation of pregnancy requires a coordinated adaptation of the immune and endocrine system. Galectins can modulate the immune responses and a member of this protein family, galectin-1 (gal-1) is abundant in the female reproductive tract and placental tissue. We hypothesized that this immunoregulatory protein might play a pivotal role in regulating fetomaternal tolerance. In the present study we found that uterine Gal-1 expression is downregulated in challenged murine pregnancies. Consistently, gal-1-/- mice exhibited increased rejection rates compared to wild-type mice even in undisturbed pregnancies (p<0.01). Treatment with recombinant Gal-1 prevented fetal rejections and restored multiple tolerance mechanisms including expansion of CD4+CD25+IL-10+ regulatory T cells in vivo, up-regulation of Th2 cytokines, increased IDO expression and activation of negative inflammatory pathways; i.e TGF-¦Â1 and Stat-3. In addition, galectin-1 promotes the generation of CD11c+ uterine DC with CD80/86lo and IL-10hi-/- mice exhibited increased rejection rates compared to wild-type mice even in undisturbed pregnancies (p<0.01). Treatment with recombinant Gal-1 prevented fetal rejections and restored multiple tolerance mechanisms including expansion of CD4+CD25+IL-10+ regulatory T cells in vivo, up-regulation of Th2 cytokines, increased IDO expression and activation of negative inflammatory pathways; i.e TGF-¦Â1 and Stat-3. In addition, galectin-1 promotes the generation of CD11c+ uterine DC with CD80/86lo and IL-10hi¦Â1 and Stat-3. In addition, galectin-1 promotes the generation of CD11c+ uterine DC with CD80/86lo and IL-10hilo and IL-10hi phenotype with a regulatory function in the development of successful pregnancies. Finally, we provide evidence for a functional cross-talk between Gal-1 and the LH/progesterone axis in the maintenance of pregnancy. The present study demonstrates a novel role for Gal-1 as a pivotal and upstream messenger in the maintenance of fetomaternal tolerance and identifies a novel therapeutic target aiming at restoring immune tolerance in threatened pregnancies : Author Disclosure Block: S.M. Blois, None; J.M. Ilarregui, None; M. Garcia, None; M.A. Toscano, None; G.A. Bianco, None; G.A. Rabinovich, None; P.C. Arck, None., None; J.M. Ilarregui, None; M. Garcia, None; M.A. Toscano, None; G.A. Bianco, None; G.A. Rabinovich, None; P.C. Arck, None., None; G.A. Bianco, None; G.A. Rabinovich, None; P.C. Arck, None. Keyword (Complete): reproductive immunology ; regulatory T cells ; dendritic cells ; Galectin-1: reproductive immunology ; regulatory T cells ; dendritic cells ; Galectin-1 Topic (Complete): AIA-09 Reproductive and newborn immunology ; ADR-11 Regulatory T cells: AIA-09 Reproductive and newborn immunology ; ADR-11 Regulatory T cells Submission Fee (Complete):: Credit Card : True: True Status: CompleteComplete Print this Page for Your Records Close Window ICI 2007 c/o Vienna Medical Academy P¨¢gina Oasis, The Online Abstract Submission System ina 1 de 2 http://www.abstractsonline.com/submit/SubmitPrinterFriendlyVersion.asp?ControlKe... 16/02/2007