Abstract
The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Several tolerance mechanisms have been studied in monocytes/macrophages contributing to scavenging, inflammation, and anti-pathogen defenses [13,14,15]
We have recently demonstrated that complement component C1q can form a multimolecular signaling complex with high mobility group box 1 (HMGB1), receptor for advanced glycation endproducts (RAGE), and Leukocyte-Associated Ig-like Receptor-1 (LAIR-1) in lipid rafts, and suppress inflammation by promoting M2-like macrophage polarization [115] (Table 1)
Summary
Failure of immune tolerance results in lymphocyte reactions against self-antigens called autoimmunity and the diseases caused by autoimmunity are referred to as autoimmune diseases. The repeated or chronic activation of Toll-like receptors (TLRs) by a bacterial product such as lipopolysaccharide (LPS) induce immune tolerance to the secondary infection [16,17,18] These mechanisms are important to prevent prolonged or repeated activation of TLRs leading to uncontrolled inflammation and subsequent damages. Ainnmti-ainnfyladmismeaasteorsytavteista, inmcliundDing(1s,e2p5-sdisi,hiysdchroexmyiav,iatartmhirnitiDs,)auinthoiimbitms uLnPeSd-iinsdeausceesd, nHeMurGodBe1gesencerreattiiovne dinisemaascerso, mpehtaabgoeslicthdroisuogrhdethrse aNnrdf2c/HanOc-e1r p[4a0th].wGayai[n3-4]a.nd loss-of-function analysis showed that Ho(fMRSAGLGEBEE1x[)4te,r1xaT]ac.LceeREllrsuxb,tlaraatarnecdHdelMtclhuyeGltaosBrse1ovblceliaocrnictDkybNaiondAfder/sewRnsNiuatlhAcdhthissaeeesnarsensoceereuaspntmtrdoarelaidfzuoiitarnotagiimndmgvmaoinnuucfnsleiaetdm/ygrmialnyta/ctthahioetuinommn[ua3ern6ni,in3dze7ep]dmr.oDoadndiusteucil-tlspHmBanfticmoeMniairistodnusaeinuGetdnnycTipicetyBH[ahmi3sta1laer,M8dlookxam]Ritlu.peGsneoAeeAglctBiaadiiuhnGbml1nsilloeaeeEaepHbdtxsntosrii,tihMndotoereaaadvnonsnGtfs,essesodrofBismrctveo,mmo1lcerituienhnreMosHlpeiesctstcdtiuDltMaotuiodhlonl2ridxGtiagnobehiitauannfBsleoontptg1rbectrcdrhmoyrkesasieemeimsn.oscnepTedtegmnbshCpLitiieHRtsuunnRorT,ndArsM4rmLir,esseGtrReGcuonaesxhE7lrBcytttReeeir1sasampapAtpntxAelcutrieGdimoeaesdlbriE,sl9niouieeacasflanxl[sonra3natttmdarehs9hmdnud]rHapa.mdiHgtltinWMeingFatMsxhea,tSGaiostitaGSahsttBcrnEurByoo1taidthmun1tocdie-attstiiiRptneimtsrvahrldAeaenteaimamhugxGcystehcuteeafEiedlonosrraysorgenilh[mntciu3eanedytt8pbverctwi,trnfr4olse,ooiaea2ikntHtvrca–thihetiins4tMvidedehoH4eeesdn]etG,pMs.orimsBrnrabbtGeop1eeioisdnucnByutihcursdh1ltio-ct.nas-pdroe-gineflnearmamtivaetodryiseaansdesa,nmti-eintaflbaomlimc datiosoryrdfuernsctainonds—canthceercr[i4ti0c]a.l Gfuaninct-ioannadl dloifsfse-roefn-fcuenmctaiyon baencaaluysseisdsbhyowHeMdGthBa1t-RHAMGGEBa1tteaxcahceedrbtaotepdartthneesremveorlietcyuolef sr.enal disease and autoimmunity in the murine model of SLE [41] Extracellular blockades such as neutralizing mouse/rat/humanized anti-HMGB1 antibodies, receptor blocking HMGB1 A box and FSSE tetramer have the distinct potential to improve clinical outcome in multiple inflammatory diseases [38,42,43,44]. Through extensive studies by others, extracellular HMGB1 is highly inclined to bind many molecules, and most other receptors are presented in a complex form with HMGB1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
