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However, the molecular mechanism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the significance of macrophage infiltration, and the correlation between Guanylate\u2010binding protein 5 (GBP5) and polarization of macrophages in rosacea\u2010like inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we tested the hypothesis that Guanylate\u2010binding protein 5 (GBP5) aggravates rosacea\u2010like skin inflammation by promoting the polarization of the M1 macrophages through the NF\u2010\u03baB signalling pathway. We depleted macrophage by injecting clodronate\u2010containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea\u2010like skin inflammation when BALB\/c mice were injected with GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5\u2010blunted M1 macrophage polarization, THP\u20101 cell was treated with GBP5 siRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Macrophage depletion ameliorated rosacea\u2010like skin inflammation in mice, implying the important role of macrophages in rosacea. Based on the transcriptome analysis, Guanylate\u2010binding protein 5 (GBP5) was identified as hub gene that was associated with macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with macrophage infiltration, the immunofluorescence analysis revealed the co\u2010localization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea\u2010like skin inflammation in the LL\u201037\u2010induced mouse model and suppressed the expression of M1 signature genes such as IL\u20106, iNOS and TNF\u2010a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF\u2010\u03baB signalling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, our study revealed the important role of macrophages in rosacea and identified GBP5 as a key regulator of rosacea by inducing M1 macrophage polarization via NF\u2010\u03baB signalling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdv.18725","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T11:10:04Z","timestamp":1668165004000},"page":"796-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["<scp>GBP5<\/scp>\n                    exacerbates rosacea\u2010like skin inflammation by skewing macrophage polarization towards\n                    <scp>M1<\/scp>\n                    phenotype through the\n                    <scp>NF\u2010\u03baB<\/scp>\n                    signalling pathway"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4647-8168","authenticated-orcid":false,"given":"Lei","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Aging Biology, Xiangya Hospital Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiangya Hospital Central South University  Changsha China"},{"name":"Hunan Key Laboratory of Aging Biology, Xiangya Hospital Central South University  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