{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:38:44Z","timestamp":1791819524976,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2023YFD1800804"],"award-info":[{"award-number":["2023YFD1800804"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pregnancy failure in the first trimester of cows significantly impacts the efficiency of the dairy industry. As a type I interferon exclusively to ruminants, IFN-\u03c4 plays a key role in maternal recognition and immune tolerance of fetuses. Macrophages are the most common immune cells within the ruminant endometrium. Nevertheless, deeply analyzing the mechanisms of IFN-\u03c4 regulating macrophage polarization still needs further study. In this study, a notable decline of bta-miR-30b-5p expression via the increase of SOCS1 was observed in uterine tissues of pregnant cows. We then confirmed that the 3\u2032UTR of SOCS1 was to be directly targeted by bta-miR-30b-5p. After that, we demonstrated that this obviously promoted the bovine macrophages (BoMac) polarized to M2 through enhancing SOCS1 expression with the treatment of IFN-\u03c4. Furthermore, we found that SOCS1 restrained the expression of the key proteins p65 and p-P65 in the NF-\u03baB pathway. Causing, the wide range of cross-species activities of IFN-\u03c4, therefore we established a pregnant mouse model for the future confirmation of the above mechanism. The results verified that IFN-\u03c4 significantly improved this mechanism and maintained normal pregnancy status in mice, but miR-30b-5p significantly reduced the M2 polarization by inhibiting SOCS1, which activated the NF-\u03baB signaling pathway, and then leading to the failure of embryo implantation. All these results indicated that IFN-\u03c4 can regulate immune tolerance during pregnancy by promoting M2 macrophage polarization through inhibiting bta-miR-30b-5p targeting SOCS1 to deactivate the NF-\u03baB signaling pathway.<\/jats:p>","DOI":"10.3390\/cells14020087","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T06:25:54Z","timestamp":1736490354000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["IFN-\u03c4 Maintains Immune Tolerance by Promoting M2 Macrophage Polarization via Modulation of Bta-miR-30b-5p in Early Uterine Pregnancy in Dairy Cows"],"prefix":"10.3390","volume":"14","author":[{"given":"Xinyu","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4153-2940","authenticated-orcid":false,"given":"Jinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-4010","authenticated-orcid":false,"given":"Bin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-927X","authenticated-orcid":false,"given":"Ganzhen","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1439-0531.2008.01171.x","article-title":"Embryonic and early foetal losses in cattle and other ruminants","volume":"43","author":"Diskin","year":"2008","journal-title":"Reprod. 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