The negative regulators of the host immune response: an unexplored pathway in preterm birth.
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).


METHODS
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.


CONCLUSIONS
Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.
Lyttle
Brianna
B
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, USA.
Chai
Jinghua
J
Gonzalez
Juan M
JM
Xu
Hua
H
Sammel
Mary
M
Elovitz
Michal A
MA
D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism; D004195:Disease Models, Animal; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D053200:Fas-Associated Death Domain Protein; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; C507772:Irak3 protein, mouse