{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:20:20Z","timestamp":1768933220517,"version":"3.49.0"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre Poland","doi-asserted-by":"crossref","award":["2017\/27\/N\/NZ5\/02756"],"award-info":[{"award-number":["2017\/27\/N\/NZ5\/02756"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maternal immune tolerance and controlled inflammatory responses are essential for fetal development and successful pregnancy. Regulatory T cells (Tregs) and B cells with regulatory properties (Bregs) maintain this balance by limiting excessive immune activation through the secretion of anti-inflammatory and tolerogenic cytokines, such as IL-10, TGF-\u03b2, and IL-35. Moreover, alterations in the costimulatory potential of antigen-presenting cells (APCs), including B cells, modulate the activation and differentiation of T cells. Toll-like receptors (TLRs), particularly TLR9, influence B-cell antigen presentation and cytokine production, thereby affecting the balance between pro-inflammatory and tolerogenic responses at the maternal\u2013fetal interface. TLR9 overexpression has been observed in several pregnancy-related disorders in both humans and murine models. In this study, we examine whether blocking TLR9 shortly after mating could improve pregnancy outcomes and modulate the regulatory and antigen-presenting functions of B cells, as well as their interactions with T cells. Using an abortion-prone murine model (CBA\/J \u00d7 DBA\/2J), we show that intraperitoneal administration of a TLR9 antagonist (ODN 2088) shortly after mating increases embryo resorption in CBA\/J females compared to controls without affecting implantation. Flow cytometry analysis further reveals that mice receiving the TLR9 antagonist are characterized by downregulation of CD80 and upregulation of CD86 on B cells, accompanied by reduced expression of CD40L and CD28 on T cells, as well as a lower percentage of Tregs and activated T cells. In conclusion, blocking TLR9 signaling shortly after mating does not improve pregnancy outcomes; conversely, it exacerbates pregnancy loss in the CBA\/J \u00d7 DBA\/2J abortion-prone model, while altering the costimulatory phenotype of B and T cells and impairing Treg development during pregnancy.<\/jats:p>","DOI":"10.3390\/ijms27020848","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:26:36Z","timestamp":1768465596000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TLR9 Inhibition Shortly After Mating Increases Fetal Resorption and Alters B- and T-Cell Costimulatory Phenotypes in an Abortion-Prone Mouse Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-3877","authenticated-orcid":false,"given":"Daria","family":"Lorek","sequence":"first","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"},{"name":"Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0804-2710","authenticated-orcid":false,"given":"Anna Ewa","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Slawek","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-4627","authenticated-orcid":false,"given":"Paulina","family":"Kubik","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Chelmonska-Soyta","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"},{"name":"Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/25785826.2020.1809951","article-title":"Harmful and Beneficial Effects of Inflammatory Response on Reproduction: Sterile and Pathogen-Associated Inflammation","volume":"44","author":"Negishi","year":"2021","journal-title":"Immunol. 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