{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:42:58Z","timestamp":1789753378553,"version":"4.0.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"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>Cysteine-rich intestinal protein 1 (CRIP1) was first identified as a metabolism-related gene nearly four decades ago, yet its precise biological function remains poorly defined. More recently, CRIP1 has been implicated in several cancers, including hepatocellular carcinoma, acute myeloid leukemia, multiple myeloma, and melanoma, where it can act as either a pro-tumorigenic factor or a tumor suppressor. In contrast, its physiological roles under non-malignant conditions have been only minimally explored, and current understanding remains largely confined to early speculative links with zinc transport and metal ion metabolism. This is the first to comprehensively dissect the basic functions of CRIP1, addressing both immune regulation and metabolism. We first sought to define CRIP1\u2019s involvement in hepatic metabolism by analyzing liver tissues from CRIP1 knockout (KO) and wild-type (WT) mice under basal conditions, focusing on zinc transport, iron metabolism, and mitochondrial oxidative phosphorylation identified through transcriptomic analysis. In parallel, we evaluated how CRIP1 deficiency modulates metabolic and immune responses under chronic low-grade inflammation induced by oral gavage with periodontal pathogens, assessing CRIP1-dependent changes. Furthermore, we investigated the relationship between CRIP1 expression and inflammatory gene profiles using single cell RNA sequencing data of peripheral mononuclear cells from healthy individuals and periodontitis patients. By comparing pro-inflammatory and anti-inflammatory gene expression according to CRIP1 expression levels across diverse immune cell subsets, we aimed to clarify whether CRIP1 is more likely to contribute to pro-inflammatory or anti-inflammatory regulation. This integrated approach provides new insights into the fundamental immunomodulatory and metabolic role of CRIP1.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1762474","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:19:14Z","timestamp":1774502354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular insights into CRIP1 as an immunometabolic regulator revealed by CRIP1 knockout and single-cell transcriptomics"],"prefix":"10.3389","volume":"17","author":[{"given":"DoYeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bok Hee","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Periodontal Disease Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Periodontal Disease Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiHye","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Ryoun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]},{"name":"Periodontal Disease Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Min","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Dental and Life Science Institute, School of Dentistry, Pusan National University","place":["Yangsan, Republic of Korea"]},{"name":"Department of Oral and Maxillofacial Surgery, Dental Research Institute, Pusan National University Dental Hospital","place":["Yangsan, Republic of 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