{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:57:08Z","timestamp":1781701028098,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\u03b22 integrins are critical for neutrophil firm adhesion, trans-endothelial migration, and the recruitment to the inflamed tissue. Autophagy is implicated in cell migration and tumor metastasis through facilitating the turnover of \u03b21 integrins; however, whether autophagy is able to control neutrophil migration by promoting the degradation of \u03b22 integrins is unexplored. Here, we show that high blood levels of palmitic acid (PA) strongly triggered neutrophil autophagy activation, leading to adhesion deficiency in dairy cows with fatty liver. The three neutrophil granule subtypes, namely, azurophil granules (AGs), specific granules (SGs), and gelatinase granules (GGs), were engulfed by the autophagosomes for degradation, resulting in an increased vacuolation in fatty liver dairy cow neutrophils. Importantly, the adhesion-associated molecules CD11b and CD18 distributed on AGs, SGs, and GGs were degraded with the three granule subtypes by autophagy. Moreover, FGA, Hsc70, and TRIM21 mediated the degradation of cytosolic oxidized\u2013ubiquitinated CD11b and CD18. Collectively, our results demonstrate that high blood PA triggers neutrophil autophagy-dependent vacuolation and granule-dependent adhesion deficiency, decreasing neutrophil mobility, and impairing the innate immune system of dairy cow with fatty liver. This theory extends the category of autophagy in maintaining granule homeostasis and provides a novel strategy to improve the immune of dairy cows with metabolic disease.<\/jats:p>","DOI":"10.3389\/fimmu.2021.726829","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T11:28:08Z","timestamp":1633692488000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Autophagy Induced by Palmitic Acid Regulates Neutrophil Adhesion Through the Granule-Dependent Degradation of \u03b1M\u03b22 Integrin in Dairy Cows With Fatty Liver"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhicheng","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiliang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochen","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500143-MCP200","article-title":"Proteomic Analysis of Human Neutrophil Granules","volume":"4","author":"Lominadze","year":"2005","journal-title":"Mol Cell Proteomics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb46237.x","article-title":"Development of Neutrophil Granule Diversity","volume":"832","author":"Borregaard","year":"1997","journal-title":"Ann NY Acad Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V65.2.423.bloodjournal652423","article-title":"Ultrastructural Localization of Lactoferrin and Myeloperoxidase in Human Neutrophils by Immunogold","volume":"65","author":"Cramer","year":"1985","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.10.3183.bloodjournal82103183","article-title":"Structural and Functional\u00a0Heterogeneity Among Peroxidase-Negative Granules in Human Neutrophils: Identification of a Distinct Gelatinase-Containing Granule Subset by Combined Immunocytochemistry and Subcellular Fractionation","author":"Kjeldsen","year":"1993","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.6.1640.1640","article-title":"Isolation and Characterization of Gelatinase Granules From Human Neutrophils","volume":"83","author":"Kjeldsen","year":"1994","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.030","article-title":"3. 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