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The Journal of Immunology, 2008, 181, 2494 -2505
Copyright © 2008 by The American Association of Immunologists, Inc.

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Uterine MHC Class I Molecules and β2-Microglobulin Are Regulated by Progesterone and Conceptus Interferons during Pig Pregnancy1

Margaret M. Joyce*,{dagger}, James R. Burghardt*,{dagger}, Robert C. Burghardt*,{dagger}, R. Neil Hooper{ddagger}, Fuller W. Bazer*,§ and Greg A. Johnson2,*,{dagger}

* Center for Animal Biotechnology and Genomics, {dagger} Department of Veterinary Integrative Bioscience, {ddagger} Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, and § Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX 77843-4458

MHC class I molecules and β2-microglobulin (β2m) are membrane glycoproteins that present peptide Ags to TCRs, and bind to inhibitory and activating receptors on NK cells and other leukocytes. They are involved in the discrimination of self from non-self. Modification of these molecules in the placenta benefits pregnancy, but little is known about their genes in the uterus. We examined the classical class I swine leukocyte Ags (SLA) genes SLA-1, SLA-2, and SLA-3, the nonclassical SLA-6, SLA-7, and SLA-8 genes, and the β2m gene in pig uterus during pregnancy. Uterine SLA and β2m increased in luminal epithelium between days 5 and 9, then decreased between days 15 and 20. By day 15 of pregnancy, SLA and β2m increased in stroma and remained detectable through day 40. To determine effects of estrogens, which are secreted by conceptuses to prevent corpus luteum regression, nonpregnant pigs were treated with estradiol benzoate, which did not affect the SLA or β2m genes. In contrast, progesterone, which is secreted by corpora lutea, increased SLA and β2m in luminal epithelium, whereas a progesterone receptor antagonist (ZK137,316) ablated this up-regulation. To determine effects of conceptus secretory proteins (CSP) containing IFN-{delta} and IFN-{gamma}, nonpregnant pigs were implanted with mini-osmotic pumps that delivered CSP to uterine horns. CSP increased SLA and β2m in stroma. Cell-type specific regulation of SLA and β2m genes by progesterone and IFNs suggests that placental secretions control expression of immune regulatory molecules on uterine cells to provide an immunologically favorable environment for survival of the fetal-placental semiallograft.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Research Initiative Grant 2006-35203-17199 from the U.S. Department of Agriculture Cooperative State Research, Education, and Extension Service and by Grant P30ES0910607 from the National Institutes of Health.

2 Address correspondence and reprint requests to Dr. Greg A. Johnson, Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4458. E-mail address: gjohnson{at}cvm.tamu.edu

3 Abbreviations used in this paper: β2m, β2-microglobulin; SLA, swine leukocyte Ag; ISG, IFN-stimulated gene; CSP, conceptus secretory protein; LE, luminal epithelium; GE, glandular epithelium; USP, ubiquitin-specific protease; IRF, IFN regulatory factor.




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