Expression of immune regulatory genes in early, mid and late stages of pig (Sus scrofa domesticus) gestation

C V RAJANI; R V PRASAD; K V JAMUNA; S SELVARAJU; G PUSHPARANI; S PARTHIPAN; J P RAVINDRA

doi:10.56093/ijans.v88i6.80882

Authors

C V RAJANI Assistant Professor, College of Veterinary and Animal Sciences, Pookode, Wayanad, Kerala
R V PRASAD Dean, Veterinary College, Shimoga, Karnataka
K V JAMUNA Professor and Head, Department of Veterinary Anatomy and Histology, Veterinary College, Bengaluru, Karnataka
S SELVARAJU ICAR National Fellow, Karnataka Veterinary Animal and Fisheries Sciences University, Bidar, Karnataka 585 401 India
G PUSHPARANI Post Doctoral Fellow, Karnataka Veterinary Animal and Fisheries Sciences University, Bidar, Karnataka 585 401 India
S PARTHIPAN Research Associate, Karnataka Veterinary Animal and Fisheries Sciences University, Bidar, Karnataka 585 401 India
J P RAVINDRA Principal Scientist and Head of Division, Reproductive Physiology Lab, Animal Physiology Division, ICAR-National Institute of Animal Nutrition and Physiology, Bengaluru.

https://doi.org/10.56093/ijans.v88i6.80882

Keywords:

Chorioallantoic membrane, FasL, MIF, Pig, TAP-1, TGFÎ²1

Abstract

Semi-allogeneic foetus and placenta exploit various mechanisms to avoid immune-mediated maternal rejection. Several factors and cytokines are attributed for production of immune tolerance during gestation and very little information on expression of these immune-regulatory genes is available in pig. Chorioallantoic membrane (CAM) from early, mid and late gestational stages (n=4) were analysed for expression of immune regulatory genes, viz. Fas ligand (FasL), transporter for antigen processing-1 (TAP-1), transforming growth factor β1 (TGF-β1) and macrophage migration inhibitory factor (MIF) whereas Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was employed as housekeeping gene. FasL gene expression was significantly higher in mid (13.46 fold) and late (28.77 fold) gestation than the early (1 fold) stage.TAP-1 mRNA expression was enhanced by 4.95 fold and 2.69 fold during mid and late gestation respectively in comparison to the early (1 fold) stage. TGF-β1 gene expression was up regulated in mid (2.43 fold) and late (2.29 fold) gestation than the early (1 fold) stage. MIF mRNA expression was enhanced in mid (3.04 fold) and late (1.59 fold) gestation in relation to the early (1 fold) stage. Placenta of pig remains entirely epitheliochorial which may minimise immune recognition and is supposed to diminish potent immune-regulatory mechanisms. However, our present study revealed consistent expression for immune regulatory factors which suggests immune modulation does exist in pig and may impart a role in pregnancy success.

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References

Andreola G, Rivoltini L, Castelli C, Huber V, Perego P, Deho P, Squarcina P, Accornero P, Lozupone F, Lugini L, Stringaro A, Molinari A, Arancia G, Gentile M, Parmiani G and Fais S. 2002. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. Journal of Experimental Medicine 195(10): 1303–16. DOI: https://doi.org/10.1084/jem.20011624

Apte R S, Sinha D, Mayhew E, Wistow G J and Niederkorn J Y. 1998. Cutting edge: Role of macrophage migration inhibitory factor in inhibiting NK cell activity and preserving immune privilege. Journal of Immunology 160: 5693–96. DOI: https://doi.org/10.4049/jimmunol.160.12.5693

Arcuri F, Cintorino M, Carducci A, Papa S, Riparbelli M G, Mangioni S, Di Blasio A M, Tosi P and Vigano P. 2006. Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor. Reproduction 131: 175–82. DOI: https://doi.org/10.1530/rep.1.00857

Aschkenazi S, Straszewski S, Verwer K M, Foellmer H, Rutherford T and Mor G. 2002. Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells. Biology of Reproduction 66(6): 1853–61. DOI: https://doi.org/10.1095/biolreprod66.6.1853

Chung E J, Choi S H, Shim Y H, Bang Y J, Hur K C and Kim C W. 2000. Transforming growth factor-beta induces apoptosis in activated murine T cells through the activation of caspase 1-like protease. Cell Immunnology 204(1): 46–54. DOI: https://doi.org/10.1006/cimm.2000.1694

Dimova T, Mihaylova A, Spassova P and Georgieva R. 2008. Superficial implantation in pigs is associated with decreased numbers and redistribution of endometrial NK-cell populations. American Journal of Reproductive Immunology 59(4): 359–69. DOI: https://doi.org/10.1111/j.1600-0897.2007.00579.x

Dong M, Ding G, Zhou J, Wang H, Zhao Y and Huang H. 2008. The effect of trophoblasts on T lymphocytes: possible regulatory effector molecules -A proteomic analysis. Cell Physiology and Biochemistry 21: 463–72. DOI: https://doi.org/10.1159/000129639

Faria M R, Hoshida M S, Av Ferro E, Ietta F, Paulesu L and Bevilacqua E. 2010. Spatiotemporal patterns of macrophage migration inhibitory factor (MIF) expression in the mouse placenta. Reproductive Biology and Endocrinology 8: 95–104. DOI: https://doi.org/10.1186/1477-7827-8-95

Frangsmyr L, Baranov V, Nagaeva O, Stendahl U, Kiellberg L and Mincheva-Nilsson L. 2005. Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to veicular level. Molecular Human Reproduction 11(1): 35–41. DOI: https://doi.org/10.1093/molehr/gah129

Hackmon R, Pinnaduwage L, Zhang J, Lye S J, Geraghty D E and Dunk C E. 2017. Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLAE, HLAC and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition. American Journal of Reproductive Immunology 77(6): e12643. DOI: https://doi.org/10.1111/aji.12643

Hsiao Y, Liao K, Hung S and Chu R. 2004. Tumor-infiltrating lymphocyte secretion of IL-6 antagonizes tumor-derived TGFb1 and restores the lymphokine-activated killing activity. Journal of Immunology 172(3): 1508–14. DOI: https://doi.org/10.4049/jimmunol.172.3.1508

Kalkunte S S, Mselle T F, Norris W E, Wira C R, Sentman C L and Sharma S. 2009. Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface. Journal of Immunology 182: 4085–92. DOI: https://doi.org/10.4049/jimmunol.0803769

Kauma S W, Huff T F, Hayes N and Nilkaeo A. 1999. Placental Fas ligand expression is a mechanism for maternal immune tolerance to the fetus. Journal of Clinical Endocrinology and Metabolism 84(6): 2188–94. DOI: https://doi.org/10.1210/jc.84.6.2188

Krockenberger M, Dombrowski Y, Weidle C, Ossadnik M, Honig A, Hausler S, Voigt H, Becker J C, Leng L, Steinle A, Weller M, Bucala R, Dietl J and Wischhusen J. 2008. Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. Journal of Immunology 180: 7338–48. DOI: https://doi.org/10.4049/jimmunol.180.11.7338

Livak K J and Schmittgen T D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2–CT method. Methods 25: 402–08. DOI: https://doi.org/10.1006/meth.2001.1262

Marrable A. 1971. The embryonic pig: A chronological account. Pitman Medical, London.

Martínez-Varea A, Pellicer B, Perales-Marín A and Pellicer A. 2014. Relationship between maternal immunological response during pregnancy and onset of preeclampsia. Journal of Immunology Research. Article ID # 210241. DOI: https://doi.org/10.1155/2014/210241

Massuto D A, Kneese E C, Johnson G A, Burghardt R C, Hooper R N, Ing N H and Jaeger L A. 2010. Transforming growth factor beta (TGFb) signalling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus-maternal interface. Reproduction 139(2): 465–78. DOI: https://doi.org/10.1530/REP-09-0447

Meyer-Siegler K L, Iczkowski K A, Leng L, Bucala R and Vera P L. 2006. Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU- 145 prostate cancer cells. Journal of Immunology 177: 8730– 39. DOI: https://doi.org/10.4049/jimmunol.177.12.8730

Mor G, Gutierrez L S, Eliza M, Kahyaoglu F and Arici A. 1998. Fas-Fas ligand system-induced apoptosis in human placenta and gestational trophoblastic disease. American Journal of Reproductive Immunology 40(2): 89–94. DOI: https://doi.org/10.1111/j.1600-0897.1998.tb00396.x

Moreau P, Paul P, Rouas-Freiss N, Kirszenbaum M, Dausset J and Carosella E D. 1998. Molecular and immunologic aspects of the nonclassical HLA class I antigen HLA-G: evidence for an important role in the maternal tolerance of the fetal allograft. American Journal of Reproductive Immunology 40(3): 136– 44. DOI: https://doi.org/10.1111/j.1600-0897.1998.tb00405.x

Motz G T, Santoro S P, Wang L, Garrabrant T, Lastra R R, Hagemann I S, Lal P, Feldman M D, Benencia F and Coukos G. 2014. Human and mice tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nature Medicine 20: 607–15. DOI: https://doi.org/10.1038/nm.3541

Nagamatsu T and Schust D J. 2010. The immunomodulatory roles of macrophages at the maternal-fetal interface. Reproductive Sciences 17(3): 209–18. DOI: https://doi.org/10.1177/1933719109349962

Paulesu L, Cateni C, Romagnoli R, Ietta F and Dantzer V. 2005. Variation in macrophage-migration-inhibitory-factor immunoreactivity during porcine gestation. Biology of Reproduction 72(4): 949–53. DOI: https://doi.org/10.1095/biolreprod.104.029058

Roh C, Lee J, Kang B, Yang S, Kim B, Bae D, Kim J and Lee J. 2002. Differential expressions of Fas and Fas ligand in human placenta. Journal of Korean Medical Science 17: 213–16. DOI: https://doi.org/10.3346/jkms.2002.17.2.213

Saito S. 2001. Cytokine cross-talk between mother and the embryo/placenta. Journal of Reproductive Immunology 52: 15– 33. DOI: https://doi.org/10.1016/S0165-0378(01)00112-7

Saito S, Umekage H, Nishikawa K, Morii T, Narita N, Enomoto M, Sakakura S, Harada N, Ichijo M and Morikawa H. 1996. Interleukin 4 (IL-4) blocks the IL-2-induced increased in natural killer activity and DNA synthesis of decidual CD16-CD56 bright NK cells by inhibiting expression of the IL-2 receptor alpha, beta, and gamma. Cell Immunology 170: 71–77. DOI: https://doi.org/10.1006/cimm.1996.0135

Stenqvist A, Nagaeva O, Baranov V and Mincheva-Nilsson L. 2013. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the foetus. Journal of Immunology 191: 5515–23. DOI: https://doi.org/10.4049/jimmunol.1301885

Sharma S. 2014. Natural killer cells and regulatory T cells in early pregnancy loss. International Journal of Developmental Biology 58: 219–29. DOI: https://doi.org/10.1387/ijdb.140109ss

Taylor A, Verhagen J, Blaser K, MübeccelAkdis M and Akdis C A. 2006. Mechanisms of immune suppression by interleukin- 10 and transforming growth factor-b: the role of T regulatory cells. Immunology 117(4): 433-42. DOI: https://doi.org/10.1111/j.1365-2567.2006.02321.x

Thellin O and Heinen E. 2003. Pregnancy and the immune system: between tolerance and rejection. Toxicology 185: 179–84. DOI: https://doi.org/10.1016/S0300-483X(02)00607-8

Tizard I R. 2009. Veterinary Immunology: An Introduction. Saunders, Philadelphia.

Vacchio M S and Hodes R J. 2005. Fetal expression of Fas ligand is necessary and sufficient for induction of CD8 T cell tolerance to the fetal antigen H-Y during pregnancy. Journal of Immunology 174: 4657–61. DOI: https://doi.org/10.4049/jimmunol.174.8.4657

Yan X, Orentas R J and Johnson B D. 2006. Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation. Cytokine 33: 188–98. DOI: https://doi.org/10.1016/j.cyto.2006.01.006

Yaddanapudi K, Rendon B E, Lamont G, Kim E J, Al Rayyan N, Richie J, Albeituni S, Waigel S, Wise A and Mitchell R A. 2016. MIF is necessary for late-stage melanoma patient MDSC immune suppression and differentiation. Cancer Immunology Research 4(2): 101–12. DOI: https://doi.org/10.1158/2326-6066.CIR-15-0070-T