Genomes and Genes
Gene Symbol: Unc93b1
Description: unc-93 homolog B1 (C. elegans)
Alias: Unc-93B1, Unc93b, protein unc-93 homolog B1, unc-93 homolog B
- Wortham B, Eppert B, Flury J, Morgado Garcia S, Borchers M. TLR and NKG2D signaling pathways mediate CS-induced pulmonary pathologies. PLoS ONE. 2013;8:e78735 pubmed publisher..Activation of these pathways plays a major role in the altered NK cell function, pulmonary inflammation and remodeling related to long-term CS exposure. ..
- Mager L, Riether C, SchÃ¼rch C, Banz Y, Wasmer M, Stuber R, et al. IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms. J Clin Invest. 2015;125:2579-91 pubmed publisher..Moreover, IL-33 improved the survival of JAK2V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs. ..
- Couillin I, Vasseur V, Charron S, Gasse P, Tavernier M, Guillet J, et al. IL-1R1/MyD88 signaling is critical for elastase-induced lung inflammation and emphysema. J Immunol. 2009;183:8195-202 pubmed publisher..In conclusion, elastase-mediated lung pathology depends on inflammasome activation with IL-1beta production. IL-1beta therefore represents a critical mediator and a possible therapeutic target of lung inflammation leading to emphysema. ..
- Franco L, Fleuri A, Pellison N, Quirino G, Horta C, de Carvalho R, et al. Autophagy downstream of endosomal Toll-like receptor signaling in macrophages is a key mechanism for resistance to Leishmania major infection. J Biol Chem. 2017;292:13087-13096 pubmed publisher..major infection. Tlr3/7/9-/- mice are as susceptible as mice deficient in MyD88 or UNC93B1, a chaperone required for appropriate localization of endosomal TLRs, but the mechanisms are unknown...
- Clingan J, Ostrow K, Hosiawa K, Chen Z, Matloubian M. Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection. J Immunol. 2012;188:4432-40 pubmed publisher..These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms. ..
- Maschalidi S, Nunes Hasler P, Nascimento C, Sallent I, Lannoy V, Garfa Traoré M, et al. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. Nat Commun. 2017;8:1640 pubmed publisher..In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol ..
- Schamber Reis B, Petritus P, Caetano B, Martinez E, Okuda K, Golenbock D, et al. UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. J Biol Chem. 2013;288:7127-36 pubmed publisherThe mammalian homolog B1 of Unc-93 Caenorhabditis elegans known as UNC93B1 is a chaperone protein that mediates translocation of the nucleic acid-sensing Toll-like receptors (TLRs) from the endoplasmic reticulum to the endolysosomes...
- Kono D, Haraldsson M, Lawson B, Pollard K, Koh Y, Du X, et al. Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus. Proc Natl Acad Sci U S A. 2009;106:12061-6 pubmed publisherUsing the Unc93b1 3d mutation that selectively abolishes nucleic acid-binding Toll-like receptor (TLR) (TLR3, -7, -9) signaling, we show these endosomal TLRs are required for optimal production of IgG autoAbs, IgM rheumatoid factor, and ..
- Mohammadi N, Midiri A, Mancuso G, Patanè F, Venza M, Venza I, et al. Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1? Production during Infection. PLoS ONE. 2016;11:e0160249 pubmed publisher..pro-IL-1? and TNF-? in these cells required the Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which is involved in mobilization of a subfamily of TLRs to the endosomes...
- Yoon J, Leyva Castillo J, Wang G, Galand C, Oyoshi M, Kumar L, et al. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med. 2016;213:2147-66 pubmed publisher..We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD. ..
- Rivas M, Koh Y, Chen A, Nguyen A, Lee Y, Lawson G, et al. MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice. J Clin Invest. 2012;122:1933-47 pubmed publisher..Moreover, microbial factors may play a substantial role in the pathogenesis of human autoimmune disease resulting from Treg deficiency. ..
- Hidmark A, von Saint Paul A, Dalpke A. Cutting edge: TLR13 is a receptor for bacterial RNA. J Immunol. 2012;189:2717-21 pubmed publisher..Although TLR7 was dispensable for cytokine induction by bRNA, TLR-associated proteins MyD88 and UNC93B were required...
- Baccala R, Welch M, Gonzalez Quintial R, Walsh K, Teijaro J, Nguyen A, et al. Type I interferon is a therapeutic target for virus-induced lethal vascular damage. Proc Natl Acad Sci U S A. 2014;111:8925-30 pubmed publisher..Thus, IFN-I may play a prominent role in hemorrhagic fevers and other acute virus infections associated with severe vascular pathology, and targeting IFN-I or downstream effector molecules may be an effective therapeutic approach. ..
- Panchanathan R, Liu H, Choubey D. Expression of murine Unc93b1 is up-regulated by interferon and estrogen signaling: implications for sex bias in the development of autoimmunity. Int Immunol. 2013;25:521-9 pubmed publisherThe endoplasmic reticulum transmembrane protein, Unc93b1, is essential for trafficking of endosomal TLRs from the endoplasmic reticulum to endosomes. A genetic defect in the human UNC93B1 gene is associated with immunodeficiency...
- Kaplan A, Ma J, Kyme P, Wolf A, Becker C, Tseng C, et al. Failure to induce IFN-? production during Staphylococcus aureus infection contributes to pathogenicity. J Immunol. 2012;189:4537-45 pubmed publisher..aureus infection (in vitro and in vivo) was protective. Together, the data demonstrate that failure to induce IFN-? production during S. aureus infection contributes to pathogenicity. ..
- Janssen E, Tabeta K, Barnes M, Rutschmann S, McBride S, Bahjat K, et al. Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway. Immunity. 2006;24:787-99 pubmed
- Taylor K, Woods T, Winkler C, Carmody A, Peterson K. Age-dependent myeloid dendritic cell responses mediate resistance to la crosse virus-induced neurological disease. J Virol. 2014;88:11070-9 pubmed publisher..Thus, this study demonstrates a reason for susceptibility to LACV infection in young animals and shows that early therapeutic treatment in young animals can prevent neurological disease. ..
- Biondo C, Malara A, Costa A, Signorino G, Cardile F, Midiri A, et al. Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis. Eur J Immunol. 2012;42:2632-43 pubmed publisher..This pathway differs from those involved in IL-23 or TNF-? responses, which we show here to be independent from translocation of intracellular TLRs, phagocytosis, or phagosomal acidification. ..
- Fukui R, Kanno A, Miyake K. Type I IFN Contributes to the Phenotype of Unc93b1D34A/D34A Mice by Regulating TLR7 Expression in B Cells and Dendritic Cells. J Immunol. 2016;196:416-27 pubmed publisher..Unc93 homolog B1 (Unc93B1) is a regulator of TLR7 that controls the TLR7 response by transporting TLR7 from the endoplasmic reticulum to ..
- Won S, Eidenschenk C, Arnold C, Siggs O, Sun L, Brandl K, et al. Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. J Virol. 2012;86:1802-8 pubmed publisher..Importantly, homozygous Eif2ak4(atc) mice showed a modest increase in susceptibility to MCMV infection, demonstrating that translational arrest dependent on GCN2 contributes to the antiviral response in vivo. ..
- Eigenbrod T, Franchi L, Muñoz Planillo R, Kirschning C, Freudenberg M, Nunez G, et al. Bacterial RNA mediates activation of caspase-1 and IL-1? release independently of TLRs 3, 7, 9 and TRIF but is dependent on UNC93B. J Immunol. 2012;189:328-36 pubmed publisher..Induction of pro-IL-1? as well as the priming for caspase-1 activation by bacterial RNA was dependent on UNC93B, an endoplasmic reticulum protein essential for delivery of TLRs to the endosome, whereas the established nucleic ..
- Castro Jorge L, Pretto C, Smith A, Foreman O, Carnahan K, Spindler K. A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis. J Virol. 2017;91: pubmed publisher..production (Pycard-/- mice) and mice defective in trafficking of Toll-like receptors to the endosome (Unc93b1-/- mice)...
- Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, et al. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Nat Commun. 2015;6:6119 pubmed publisher..Spontaneous TLR7 activation in Unc93b1(D34A/D34A) mice causes lethal inflammation...
- Tchaptchet S, Gumenscheimer M, Kalis C, Freudenberg N, Holscher C, Kirschning C, et al. TLR9-dependent and independent pathways drive activation of the immune system by Propionibacterium acnes. PLoS ONE. 2012;7:e39155 pubmed publisher..acnes effects seems unlikely and the participation of the known MyD88-dependent receptors, including TLR5, Unc93B-dependent TLRs, IL-1R and IL-18R in the development of the alternative response has been excluded...
- Han J, Akira S, Calame K, Beutler B, Selsing E, Imanishi Kari T. Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Immunity. 2007;27:64-75 pubmed..Early AID expression can increase the preimmune repertoire of developing B cells, may provide an innate population of IgG- and IgA-expressing cells, and could be involved in receptor editing of self-reactive immature B cells. ..
- Baccarella A, Fontana M, Chen E, Kim C. Toll-like receptor 7 mediates early innate immune responses to malaria. Infect Immun. 2013;81:4431-42 pubmed publisher..Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses. ..
- Tarallo V, Hirano Y, Gelfand B, Dridi S, Kerur N, Kim Y, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell. 2012;149:847-59 pubmed publisher..Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements. ..
- Kim J, Huh J, Hwang M, Kwon E, Jung D, Brinkmann M, et al. Acidic amino acid residues in the juxtamembrane region of the nucleotide-sensing TLRs are important for UNC93B1 binding and signaling. J Immunol. 2013;190:5287-95 pubmed publisher..The polytopic membrane protein UNC93B1 physically interacts with the nucleotide-sensing TLRs and delivers them from the endoplasmic reticulum to ..
- Pollard K, Escalante G, Huang H, Haraldsson K, Hultman P, Christy J, et al. Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN. J Immunol. 2017;199:3739-3747 pubmed publisher..that require type I IFN signaling for spontaneous disease, but was dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton transporter, solute carrier family 15, member 4...
- Bashratyan R, Sheng H, Regn D, Rahman M, Dai Y. Insulinoma-released exosomes activate autoreactive marginal zone-like B cells that expand endogenously in prediabetic NOD mice. Eur J Immunol. 2013;43:2588-97 pubmed publisher..Thus, EXOs may contribute to the development of autoimmunity and type 1 diabetes in NOD mice, partially via activating autoreactive marginal zone-like B cells. ..
- Lafferty E, Flaczyk A, Angers I, Homer R, d Hennezel E, Malo D, et al. An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection. Genes Immun. 2014;15:320-32 pubmed publisher..Using N-ethyl-N-nitrosourea mutagenesis, we created a recessive loss-of-function point mutation in Unc93b1 (unc-93 homolog B1 (C...
- Silva Barrios S, Smans M, Duerr C, Qureshi S, Fritz J, Descoteaux A, et al. Innate Immune B Cell Activation by Leishmania donovani Exacerbates Disease and Mediates Hypergammaglobulinemia. Cell Rep. 2016;15:2427-37 pubmed publisher..donovani is responsible for disease exacerbation through IL-10 and IFN-I production and for the promotion of hypergammaglobulinemia. ..
- Yu P, Lübben W, Slomka H, Gebler J, Konert M, Cai C, et al. Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity. 2012;37:867-79 pubmed publisher..Our study suggests that in addition to their role in innate immunity against exogenous pathogens, nucleic acid-recognizing TLRs contribute to the immune control of activated ERVs and ERV-induced tumors...
- Huh J, Shibata T, Hwang M, Kwon E, Jang M, Fukui R, et al. UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5. Proc Natl Acad Sci U S A. 2014;111:7072-7 pubmed publisher..of the nucleotide-sensing TLRs from the endoplasmic reticulum to the endolysosomes strictly depends on UNC93B1, and their signaling is completely abolished in the 3d mutant mice bearing the H412R mutation of UNC93B1...
- Xu P, Grueter B, Britt J, McDaniel L, Huntington P, Hodge R, et al. Double deletion of melanocortin 4 receptors and SAPAP3 corrects compulsive behavior and obesity in mice. Proc Natl Acad Sci U S A. 2013;110:10759-64 pubmed publisher..Our findings offer insights into the pathophysiology and treatment of both compulsive behavior and eating disorders. ..
- Eidenschenk C, Crozat K, Krebs P, Arens R, Popkin D, Arnold C, et al. Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells. Proc Natl Acad Sci U S A. 2010;107:9759-64 pubmed publisher..In the absence of Flt3 signaling, NK cell activation is delayed and survival during MCMV infection is markedly compromised. ..
- Roberts A, Lee B, Deguine J, John S, Shlomchik M, Barton G. Tissue-Resident Macrophages Are Locally Programmed for Silent Clearance of Apoptotic Cells. Immunity. 2017;47:913-927.e6 pubmed publisher..The coordinated expression of AC receptors with genes that limit responses to nucleic acids might ensure maintenance of homeostasis and thus represent a central feature of tissue macrophages. ..
- Choo M, Sano Y, Kim C, Yasuda K, Li X, Lin X, et al. TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects. J Exp Med. 2017;214:1297-1311 pubmed publisher..Our study suggests a role for bacterial spore-associated RNA in microbial pathogenesis and illustrates a little known aspect of interactions between the host and spore-forming bacteria. ..
- Clingan J, Matloubian M. B Cell-intrinsic TLR7 signaling is required for optimal B cell responses during chronic viral infection. J Immunol. 2013;191:810-8 pubmed publisher..These results suggest that B cell-intrinsic TLR signaling in vivo likely affects plasma cell output by altered selection of Ag-specific B cells in the GC. ..
- Crane M, Gaddi P, Salazar Mather T. UNC93B1 mediates innate inflammation and antiviral defense in the liver during acute murine cytomegalovirus infection. PLoS ONE. 2012;7:e39161 pubmed publisher..We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine ..
- Hoebe K, Du X, Goode J, Mann N, Beutler B. Lps2: a new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening. J Endotoxin Res. 2003;9:250-5 pubmed..The Lps2 mutation does not preclude signaling initiated by peptidoglycan or unmethylated DNA. Hence, genetic data suggest that there is at least one 'missing' component of the LPS receptor complex that has yet to be found. ..
- Lee B, Moon J, Shu J, Yuan L, Newman Z, Schekman R, et al. UNC93B1 mediates differential trafficking of endosomal TLRs. elife. 2013;2:e00291 pubmed publisherb>UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes...
- Avalos A, Kirak O, Oelkers J, Pils M, Kim Y, Ottinger M, et al. Cell-specific TLR9 trafficking in primary APCs of transgenic TLR9-GFP mice. J Immunol. 2013;190:695-702 pubmed publisher..Both processes depend on interactions of TLR9 with the polytopic endoplasmic reticulum-resident protein UNC93B1. To examine the intracellular behavior of TLR9 in primary APCs, we generated transgenic mice expressing a TLR9-..
- Caetano B, Carmo B, Melo M, Cerny A, Dos Santos S, Bartholomeu D, et al. Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi. J Immunol. 2011;187:1903-11 pubmed publisherb>UNC93B1 associates with TLR3, 7, and 9, mediating their translocation from the endoplasmic reticulum to the endolysosome, thus allowing proper activation by microbial nucleic acids...
- Wang J, Jeelall Y, Beutler B, Horikawa K, Goodnow C. Consequences of the recurrent MYD88(L265P) somatic mutation for B cell tolerance. J Exp Med. 2014;211:413-26 pubmed publisher..The mutation induced rapid B cell division in the absence of exogenous TLR ligands and was inhibited by Unc93b1(3d) mutation and chloroquine or TLR9 deficiency, indicating continued dependence on upstream TLR9 activation...
- Koh Y, Scatizzi J, Gahan J, Lawson B, Baccala R, Pollard K, et al. Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells. J Immunol. 2013;190:4982-90 pubmed publisher..Using Unc93b1(3d) lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear autoantibody ..
- Cook M, Vinuesa C, Goodnow C. ENU-mutagenesis: insight into immune function and pathology. Curr Opin Immunol. 2006;18:627-33 pubmed..More than 20 of the phenotypes that exhibit a simple (Mendelian) pattern of inheritance have been mapped. Novel alleles have revealed new pathways of host defense, allergy and autoimmunity. ..
- Sweeney T, Suliman H, Hollingsworth J, Welty Wolf K, Piantadosi C. A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators in mice with Staphylococcal aureus sepsis. PLoS ONE. 2011;6:e25249 pubmed publisher..because neither gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were activated normally in Unc93b1-deficient (3d) mice...
- Lafferty E, Wiltshire S, Angers I, Vidal S, Qureshi S. Unc93b1 -Dependent Endosomal Toll-Like Receptor Signaling Regulates Inflammation and Mortality during Coxsackievirus B3 Infection. J Innate Immun. 2015;7:315-30 pubmed publisher..we studied mice with a loss-of-function mutation, known as Letr for 'loss of endosomal TLR response', in Unc93b1, which is a chaperone protein for TLR3, TLR7 and TLR9...
- Kawashima T, Kosaka A, Yan H, Guo Z, Uchiyama R, Fukui R, et al. Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-?. Immunity. 2013;38:1187-97 pubmed publisher..These results identify TLR3 as a sensor to small intestinal commensal bacteria and suggest that dsRNA in commensal bacteria contributes to anti-inflammatory and protective immune responses. ..