The negative regulators of the host immune response: an unexplored pathway in preterm birth
Presented at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Jan. 26-31, 2009.
Received 27 February 2009; received in revised form 21 April 2009; accepted 27 May 2009.
Objective
Toll-like receptors (TLRs) are essential mediators of host immunity. TLR activation must be tightly regulated to prevent an exaggerated immune response from devastating the host. These studies assessed the expression of negative regulators (interleukin receptor-associated kinase [IRAK]-3, IRAK-1, Fas-associated protein with death domain) during pregnancy and in preterm birth (PTB).
Study Design
Tissues (uterine, cervix, placenta, and spleens) from the following experimental groups were harvested: (1) nonpregnant mice, (2) pregnant mice across gestation, (3) murine model of PTB, and (4) pregnant mice exposed to medroxyprogesterone acetate (MPA).
Results
Negative regulators are differentially expressed in the uterus during pregnancy. In the setting of PTB, IRAK-3 is significantly increased in the uterus and cervix but not the placenta. In maternal spleens, IRAK-3 and IRAK-1 are increased in response to intrauterine inflammation. MPA can increase IRAK expression in cervical tissues.
Conclusion
Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.
Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, PA
This study was supported in part by March of Dimes Grants 6-FY06-312 and R01HD046544-05.
Reprints not available from the authors.
Cite this article as: Lyttle B, Chai J, Gonzalez JM, et al. The negative regulators of the host immune response: an unexplored pathway in preterm birth. Am J Obstet Gynecol 2009;201:284.e1-7.
ABSTRACT
The negative regulators of the host immune response: an unexplored pathway in preterm birth