{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T13:13:41Z","timestamp":1786799621186,"version":"build-2736575974"},"reference-count":52,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":574,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["Z01 ES102005"],"award-info":[{"award-number":["Z01 ES102005"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1074\/jbc.ra118.004300","type":"journal-article","created":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T23:55:17Z","timestamp":1544140517000},"page":"1997-2008","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response"],"prefix":"10.1016","volume":"294","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2142-4182","authenticated-orcid":false,"given":"Jim J.","family":"Aloor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Azzam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-8628","authenticated-orcid":false,"given":"John J.","family":"Guardiola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kymberly M.","family":"Gowdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H.","family":"Madenspacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin A.","family":"Gabor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Chi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artiom","family":"Gruzdev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Draper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Alex","family":"Merrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Fessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.RA118.004300_bib1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"10.1074\/jbc.RA118.004300_bib2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.smim.2003.10.006","article-title":"Toll-like receptors and acquired immunity","volume":"16","author":"Pasare","year":"2004","journal-title":"Semin. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrd3203","article-title":"Targeting Toll-like receptors: emerging therapeutics?","volume":"9","author":"Hennessy","year":"2010","journal-title":"Nat. Rev. Drug Discov"},{"key":"10.1074\/jbc.RA118.004300_bib5","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nri3151","article-title":"Accessory molecules for Toll-like receptors and their function","volume":"12","author":"Lee","year":"2012","journal-title":"Nat. Rev. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib6","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/nature07830","article-title":"The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex","volume":"458","author":"Park","year":"2009","journal-title":"Nature"},{"key":"10.1074\/jbc.RA118.004300_bib7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.chom.2008.12.002","article-title":"RP105 facilitates macrophage activation by Mycobacterium tuberculosis lipoproteins","volume":"5","author":"Blumenthal","year":"2009","journal-title":"Cell Host Microbe"},{"key":"10.1074\/jbc.RA118.004300_bib8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/ni1198","article-title":"Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105","volume":"6","author":"Divanovic","year":"2005","journal-title":"Nat. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib9","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.4049\/jimmunol.0901518","article-title":"TRIL, a functional component of the TLR4 signaling complex, highly expressed in brain","volume":"183","author":"Carpenter","year":"2009","journal-title":"J. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib10","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.immuni.2006.12.005","article-title":"Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages","volume":"26","author":"Yang","year":"2007","journal-title":"Immunity"},{"key":"10.1074\/jbc.RA118.004300_bib11","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1084\/jem.20071132","article-title":"A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses","volume":"204","author":"Takahashi","year":"2007","journal-title":"J. Exp. Med"},{"key":"10.1074\/jbc.RA118.004300_bib12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/ni1297","article-title":"The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9","volume":"7","author":"Tabeta","year":"2006","journal-title":"Nat. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1074\/mcp.M800286-MCP200","article-title":"Quantitative proteomics analysis of macrophage rafts reveals compartmentalized activation of the proteasome and of proteasome-mediated ERK activation in response to lipopolysaccharide","volume":"8","author":"Dhungana","year":"2009","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1074\/jbc.RA118.004300_bib14","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"10.1074\/jbc.RA118.004300_bib15","first-page":"166","article-title":"TMBASE: a database of membrane spanning protein segments","volume":"374","author":"Hofmann","year":"1993","journal-title":"Biol. Chem. Hoppe-Seyler"},{"key":"10.1074\/jbc.RA118.004300_bib16","doi-asserted-by":"crossref","first-page":"e1000213","DOI":"10.1371\/journal.pcbi.1000213","article-title":"Transmembrane topology and signal peptide prediction using dynamic bayesian networks","volume":"4","author":"Reynolds","year":"2008","journal-title":"PLoS Comput. Biol"},{"key":"10.1074\/jbc.RA118.004300_bib17","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/1471-2164-8-320","article-title":"The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns","volume":"8","author":"Dolan","year":"2007","journal-title":"BMC Genomics"},{"issue":"Suppl. 1","key":"10.1074\/jbc.RA118.004300_bib18","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1073\/pnas.1000093107","article-title":"Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity","volume":"108","author":"Ng","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.RA118.004300_bib19","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1093\/bioinformatics\/btp302","article-title":"pGenTHREADER and pDomTHREADER: new methods for improved protein fold recognition and superfamily discrimination","volume":"25","author":"Lobley","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1074\/jbc.RA118.004300_bib20","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.sbi.2008.10.003","article-title":"Novel structural insights into F-actin-binding and novel functions of calponin homology domains","volume":"18","author":"Sj\u00f6blom","year":"2008","journal-title":"Curr. Opin. Struct. Biol"},{"key":"10.1074\/jbc.RA118.004300_bib21","doi-asserted-by":"crossref","first-page":"e12257","DOI":"10.1371\/journal.pone.0012257","article-title":"LRCH proteins: a novel family of cytoskeletal regulators","volume":"5","author":"Foussard","year":"2010","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.004300_bib22","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1042\/BJ20121528","article-title":"PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains","volume":"453","author":"Gokhale","year":"2013","journal-title":"Biochem. J"},{"key":"10.1074\/jbc.RA118.004300_bib23","doi-asserted-by":"crossref","first-page":"7016","DOI":"10.1073\/pnas.0802405105","article-title":"Identification of innate immunity genes and pathways using a comparative genomics approach","volume":"105","author":"Alper","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.RA118.004300_bib24","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature07548","article-title":"Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein","volume":"457","author":"Trompette","year":"2009","journal-title":"Nature"},{"key":"10.1074\/jbc.RA118.004300_bib25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1152\/physiolgenomics.00128.2004","article-title":"The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades","volume":"19","author":"Bj\u00f6rkbacka","year":"2004","journal-title":"Physiol. Genomics"},{"key":"10.1074\/jbc.RA118.004300_bib26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling","volume":"7","author":"O'Neill","year":"2007","journal-title":"Nat. Rev. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib27","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1161\/CIRCULATIONAHA.108.793869","article-title":"Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions","volume":"118","author":"Yvan-Charvet","year":"2008","journal-title":"Circulation"},{"key":"10.1074\/jbc.RA118.004300_bib28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jaci.2014.01.032","article-title":"APO\u03f54 is associated with enhanced in vivo innate immune responses in human subjects","volume":"134","author":"Gale","year":"2014","journal-title":"J. Allergy Clin. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib29","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1242\/jcs.115.12.2603","article-title":"Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation","volume":"115","author":"Triantafilou","year":"2002","journal-title":"J. Cell Sci"},{"key":"10.1074\/jbc.RA118.004300_bib30","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.4049\/jimmunol.1100253","article-title":"Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling","volume":"187","author":"Fessler","year":"2011","journal-title":"J. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib31","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1096\/fj.06-6661com","article-title":"VEGF-induced heme oxygenase-1 confers cytoprotection from lethal hyperoxia in vivo","volume":"21","author":"Siner","year":"2007","journal-title":"FASEB J"},{"key":"10.1074\/jbc.RA118.004300_bib32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/sj.mt.6300309","article-title":"Lentiviral-mediated GATA-3 RNAi decreases allergic airway inflammation and hyperresponsiveness","volume":"16","author":"Lee","year":"2008","journal-title":"Mol. Ther"},{"key":"10.1074\/jbc.RA118.004300_bib33","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1084\/jem.20121674","article-title":"p53 Integrates host defense and cell fate during bacterial pneumonia","volume":"210","author":"Madenspacher","year":"2013","journal-title":"J. Exp. Med"},{"key":"10.1074\/jbc.RA118.004300_bib34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/1471-2180-10-100","article-title":"Virulence-related Mycobacterium avium subsp. hominissuis MAV_2928 gene is associated with vacuole remodeling in macrophages","volume":"10","author":"Jha","year":"2010","journal-title":"BMC Microbiol"},{"key":"10.1074\/jbc.RA118.004300_bib35","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1073\/pnas.0811073106","article-title":"MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells","volume":"106","author":"Ceppi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.RA118.004300_bib36","doi-asserted-by":"crossref","first-page":"e3024","DOI":"10.1371\/journal.pone.0003024","article-title":"Transcriptome-wide assessment of human brain and lymphocyte senescence","volume":"3","author":"Hong","year":"2008","journal-title":"PLoS One"},{"key":"10.1074\/jbc.RA118.004300_bib37","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ni1207","article-title":"CD14 is required for MyD88-independent LPS signaling","volume":"6","author":"Jiang","year":"2005","journal-title":"Nat. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.molimm.2014.05.008","article-title":"Toll-like receptor co-receptors as master regulators of the immune response","volume":"63","author":"Di Gioia","year":"2015","journal-title":"Mol. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib39","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4049\/jimmunol.0802909","article-title":"Soluble TLR2 reduces inflammation without compromising bacterial clearance by disrupting TLR2 triggering","volume":"183","author":"Raby","year":"2009","journal-title":"J. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib40","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/jlb.67.6.894","article-title":"cAMP induces CD14 expression in murine macrophages via increased transcription","volume":"67","author":"Liu","year":"2000","journal-title":"J. Leukocyte Biol"},{"key":"10.1074\/jbc.RA118.004300_bib41","doi-asserted-by":"crossref","first-page":"7823","DOI":"10.4049\/jimmunol.174.12.7823","article-title":"STAT-1 mediates the stimulatory effect of IL-10 on CD14 expression in human monocytic cells","volume":"174","author":"Rahimi","year":"2005","journal-title":"J. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0378-1119(00)00179-7","article-title":"Characterization of rat CD14 promoter and its regulation by transcription factors AP1 and Sp family proteins in hepatocytes","volume":"250","author":"Liu","year":"2000","journal-title":"Gene"},{"key":"10.1074\/jbc.RA118.004300_bib43","doi-asserted-by":"crossref","first-page":"23242","DOI":"10.1074\/jbc.274.33.23242","article-title":"CCAAT\/enhancer-binding protein activates the CD14 promoter and mediates transforming growth factor \u03b2 signaling in monocyte development","volume":"274","author":"Pan","year":"1999","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.004300_bib44","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.1172\/JCI57559","article-title":"ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice","volume":"121","author":"Murphy","year":"2011","journal-title":"J. Clin. Invest"},{"key":"10.1074\/jbc.RA118.004300_bib45","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1161\/ATVBAHA.108.168690","article-title":"High-density lipoprotein reduces the human monocyte inflammatory response","volume":"28","author":"Murphy","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol"},{"key":"10.1074\/jbc.RA118.004300_bib46","doi-asserted-by":"crossref","first-page":"22930","DOI":"10.1074\/jbc.M801408200","article-title":"Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages","volume":"283","author":"Zhu","year":"2008","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.RA118.004300_bib47","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1194\/jlr.M006486","article-title":"Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol","volume":"51","author":"Zhu","year":"2010","journal-title":"J. Lipid Res"},{"key":"10.1074\/jbc.RA118.004300_bib48","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1186\/1743-422X-8-479","article-title":"Research advances on flotillins","volume":"8","author":"Zhao","year":"2011","journal-title":"Virol. J"},{"key":"10.1074\/jbc.RA118.004300_bib49","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol"},{"key":"10.1074\/jbc.RA118.004300_bib50","doi-asserted-by":"crossref","first-page":"4.21.1","DOI":"10.1002\/0471142301.ns0421s37","article-title":"Production and titration of lentiviral vectors","volume":"37","author":"Salmon","year":"2006","journal-title":"Curr. Protoc. Neurosci"},{"key":"10.1074\/jbc.RA118.004300_bib51","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc"},{"key":"10.1074\/jbc.RA118.004300_bib52","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1093\/bioinformatics\/bth195","article-title":"The DISOPRED server for the prediction of protein disorder","volume":"20","author":"Ward","year":"2004","journal-title":"Bioinformatics"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820368459?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820368459?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.RA118.004300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T08:18:56Z","timestamp":1641284336000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820368459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["S0021925820368459"],"URL":"https:\/\/doi.org\/10.1074\/jbc.ra118.004300","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2019,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1074\/jbc.RA118.004300","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"name":"copyright","label":"Copyright"}]}}