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Article

CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model

1
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
2
Polpharma Biologics SA, Trzy Lipy 3, 80-172 Gdańsk, Poland
3
Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Dariusz Szukiewicz
Int. J. Mol. Sci. 2021, 22(14), 7296; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147296
Received: 28 May 2021 / Revised: 29 June 2021 / Accepted: 5 July 2021 / Published: 7 July 2021
(This article belongs to the Special Issue Reproductive Immunology and Pregnancy 2.0)
The loss of immune tolerance to fetal antigens may result in reproductive failure. The downregulated number and activity of T regulatory lymphocytes, which are critical for the establishment of immune tolerance to fetal antigens, during pregnancy may lead to miscarriage. The adoptive transfer of Tregs prevents fetal loss in abortion-prone mice. Recently, we demonstrated that the administration of tregitopes, which are short peptides found in human and mouse immunoglobulins (IgGs), decreased the incidence of abortions in female CBA/J mice mated with DBA/2J mice. Here, two non-IgG source peptides (SGS and LKD) that can potentially bind to the major histocompatibility complex II (MHC II) with high affinity and induce Treg expansion were designed in silico. The immune dysregulation-induced pregnancy failure mouse model was used to evaluate the effect of SGS and LKD on immune response and pregnancy outcome. The fetal death rate in the SGS-treated group was lower than that in the phosphate-buffered saline-treated group. SGS and LKD upregulated the splenic pool of Tregs and modulated the T-helper cell (Th1)/Th2-related cytokine response at the preimplantation stage. Additionally, SGS and LKD downregulated the expression of CD80 and MHC class II molecules in splenic CD11c+ antigen-presenting cells. Thus, SGS treatment can result in beneficial pregnancy outcomes. Additionally, SGS peptide-mediated immunomodulation can be a potential therapeutic strategy for immune dysregulation-induced pregnancy failure. View Full-Text
Keywords: tregs; bregs; pregnancy; epitope; CD80; CD86; antigen-presenting cells; miscarriage; MHCII; CD91 tregs; bregs; pregnancy; epitope; CD80; CD86; antigen-presenting cells; miscarriage; MHCII; CD91
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MDPI and ACS Style

Kedzierska, A.E.; Lorek, D.; Slawek, A.; Grabowski, T.; Chelmonska-Soyta, A. CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model. Int. J. Mol. Sci. 2021, 22, 7296. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147296

AMA Style

Kedzierska AE, Lorek D, Slawek A, Grabowski T, Chelmonska-Soyta A. CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model. International Journal of Molecular Sciences. 2021; 22(14):7296. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147296

Chicago/Turabian Style

Kedzierska, Anna E., Daria Lorek, Anna Slawek, Tomasz Grabowski, and Anna Chelmonska-Soyta. 2021. "CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model" International Journal of Molecular Sciences 22, no. 14: 7296. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147296

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