IL6R，全稱為白細(xì)胞介素6受體，是一種調(diào)節(jié)免疫細(xì)胞生長(zhǎng)和轉(zhuǎn)化的膜受體。研究表明，IL6R在許多疾病中發(fā)揮重要作用，包括類風(fēng)濕性關(guān)節(jié)炎、系統(tǒng)性紅斑狼瘡、多發(fā)性骨髓瘤等。最近的研究還發(fā)現(xiàn)，IL6R可能與新型冠狀病毒感染的嚴(yán)重程度相關(guān)。

Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis. The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).; Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells.; Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity. The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases. In complex with IL6, is required for induction of VEGF production. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis.; Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity. The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases. In complex with IL6, is required for induction of VEGF production. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis.

1. The AA genotype for IL6R rs12083537 and CC for rs11265618 polymorphisms for may act as predictors of good response LDA. PMID: 27958380
2. a significant negative correlation of meprin beta expression and IL-6R levels on human granulocytes, providing evidence for in vivo function of this proteolytic interaction. PMID: 28276471
3. IL-6/soluble IL-6R differentially regulate RANKL-induced osteoclast differentiation and activity through modulation of NF-kappaB, ERK and JNK signaling pathways. PMID: 28128332
4. Gene IL6R polymorphic variant rs2228145(C>A) seems to be involved in genetic predisposition of the population of Karelia to nonalcoholic steatohepatitis. PMID: 29797122
5. IL-6R was shown to be an independent prognostic factor for patients with cervical cancer. PMID: 28741286
6. Frequency of IL-6R TT (rs4129267) genotype was increased in Ankylosing Spondylitis patients. Interleukin IL-6R (rs4129267) gene polymorphisms could serve as promising biomarkers for diagnosis and prognosis in Ankylosing Spondylitis patients. PMID: 29200018
7. In a genome-wide meta-analysis of 20,550 patients with Crohn's disease (CD), 17,647 patients with ulcerative colitis (UC), and more than 40,000 individuals without IBD (controls), study found that rs2228145 (scaled to a 2-fold increase in s-IL6R) was associated with reduced risk of CD or UC.[meta-analysis] PMID: 29775600
8. Analysis of the IL-6 (-572G/C) polymorphism revealed a higher level of the GG genotype in the patients with Celiac Disease compared with the control group. PMID: 28928101
9. miR-124, IL-6R and STAT3 are involved in the process of sulforaphane-improved CDDP chemotherapy efficacy by targeting cancer stem cell-like properties PMID: 27824145
10. High IL6-R expression is associated with cisplatin resistance in epithelial ovarian cancer. PMID: 28388577
11. sIL-6R may be a useful biomarker to assess insulin resistance among morbidly obese subjects PMID: 28346858
12. Study identified variants associated with the age of onset of Alzheimer's disease in APOE varepsilon4 carriers. Across five datasets, p.D358A had a meta P = 3 x10-4 and an odds ratio = 1.3, 95% confidence interval 1.12 -1.48. Study suggests that a common coding region variant of the IL-6 receptor results in neuroinflammatory changes that may influence the age of onset of Alzheimer's disease in APOE varepsilon4 carriers. PMID: 28106546
13. IL-6R protein expression on plasma membrane of ovarian cancer cells mediates enhanced cell migration/invasiveness in response to IL6 in ascites. PMID: 27825119
14. IL6R protein levels were higher in bone than in lymph node and visceral metastases of castration-resistant prostate cancer. PMID: 27344294
15. IL-6R CC genotype was associated with a three times greater concussion risk and APOE4 with a 40% lower risk in college athletes PMID: 28918391
16. In the present study, the authors show that deletion of a triple serine (3S) motif (Ser-359 to Ser-361) adjacent to the cleavage site is sufficient to prevent IL-6R cleavage by ADAM17, but not ADAM10. We find that the impaired shedding is caused by the reduced distance between the cleavage site and the plasma membrane. PMID: 27151651
17. IL6R SNPs are associated with simultaneously high CRP, LDL and ApoB levels. PMID: 28769070
18. CLL cells with higher CD126 expression are more resistant to treatment. PMID: 26712690
19. The mRNA expression of IL6R was inversely correlated with miR-449a in osteosarcoma tissues. In addition, JAK1/STAT3 signaling pathway was regulated by circ_0009910/miR-449a/IL6R axis. PMID: 29117539
20. IL-6 receptor blockade has an effect on high-sensitivity troponin T and NT-proBNP in rheumatoid arthritis PMID: 27744141
21. Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124. PMID: 29120300
22. we present evidence for the role of M2 phenotype TAM in IL-6 receptor-mediated signals, particularly tyrosine phosphorylation of STAT3, responsible for the prosurvival adaptation of tumor cells to hypoxia. PMID: 26705936
23. 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. PMID: 27078193
24. The expression of STOML2, a gene that plays a key role in mitochondrial function and T-cell activation, is associated with both IL-6 signaling and asthma risk. PMID: 26932604
25. IL6R is downregulated in the tissues from colonic biopsies taken from Ulcerative Colitis patients.Thus, expression levels of IL6R can be used as markers of disease or disease progression in Ulcerative Colitis patients. PMID: 28774868
26. expanded CD8(+)IL-6Ralpha(low) EM T cells have roles in coronary artery disease through their pro-inflammatory and highly cytotoxic capacities PMID: 27062409
27. Both gingival crevicular fluid sIL-6R and calprotectin concentrations are significant biomarkers in the evaluation of periodontal inflammation PMID: 27810997
28. Our results argued that increased expression of sIL6R from myeloid cells and subsequent c-Maf induction were adverse events for counteracting tumor-specific Th1 generation. Overall, this work provides a mechanistic rationale for sIL6R targeting to improve the efficacy of T-cell-mediated cancer immunotherapy PMID: 28235765
29. These results demonstrate a novel physiologic role for a disintegrin and metalloprotease 17 in regulating murine IL-6 signals during inflammatory processes. PMID: 26561568
30. this study show that soluble IL-6R is infiltrating from the circulation in an ADAM17-independent process and is involved in the controlled resolution of an acute inflammatory episode PMID: 27698010
31. the sIL-6R/p28 fusion protein (FP) upregulated IFN-lambda1 expression by increasing the binding abilities of c-Fos and activating transcription factor 1 to the IFN-lambda1 promoter via the p38 MAPK signaling pathway; results demonstrate the important role of sIL-6R/p28 FP in mediating virus-induced type III IFN production PMID: 27527594
32. Soluble IL-6R levels appeared to be significantly higher irrespective of disease activity in patients with large-vessel vasculitis. PMID: 28466804
33. glycosylation is an important regulator for soluble IL-6R generation. PMID: 28060820
34. IL-6R rs2228145 genotype was associated with decreased risk of gastric cancer for the individuals with negative and positive Helicobacter pylori infection. PMID: 28442395
35. The here presented data demonstrate that miR-451 may function as a potential suppressor of tumor growth, migration and angiogenesis in osteosarcoma via down-regulating IL 6R. PMID: 27908732
36. DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of ischemic heart disease. PMID: 26981890
37. minor allele, with the difference eliminated upon addition of tocilizumab. In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells.d However, we were unable to identify evidence for aisease PMID: 28334838
38. MiR-451 may function as a potential suppressor of tumor angiogenesis in HCC by targeting IL-6R-STAT3-VEGF signaling, suggesting. PMID: 27461244
39. high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes. PMID: 27460086
40. No significant association between IL6R rs2228145 and dementia. PMID: 26725994
41. Rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with ischemic stroke. PMID: 26955245
42. Data suggest domains D1-D3, which contain cytokine binding module, determine which cytokine can activate interleukin-6 or interleukin-11 alpha-receptor subunits; stalk, transmembrane, or intracellular regions do not participate in ligand selectivity. PMID: 26551279
43. Anti-IL-6R antibody prevented the early loss of intrahepatic islet grafts mediated by HMGB1-induced immune activation after islet transplantation. PMID: 25058889
44. While prior studies have found an association between PDE4D and IL6R polymorphisms and ischemic stroke, the results of this study suggest that this association may be different in a hypertensive population. PMID: 26782593
45. Authors identified miR-125a as a direct regulator of IL-6R, and the genotype of rs12976445 might be a novel predictor of the development of DN in DM. PMID: 26563755
46. results provide evidence that two IL6R gene polymorphisms rs2228145 C and rs12083537 G are associated with poor lung function in patients with asthma. Furthermore, the rs2228145 A-C variant is associated with levels of sIL-6R and IgE. PMID: 26997259
47. miR-125a-5p directly targets IL-6R and STAT3 expression in HEK-293T cells. PMID: 26424054
48. High serum IL-6R levels were associated with Chronic Spontaneous Urticaria. PMID: 26699882
49. findings identify TRAF3 and PTPN22 as inhibitors of IL-6R signaling in B cells and reveal a previously uncharacterized role for TRAF3 in the regulation of plasma cell differentiation PMID: 26329582
50. Interleukin-6 is strongly affected by factors associated with obesity accounting for its lability and responsiveness to diet, life style and contemporaneous events. PMID: 26086344

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[Isoform 1]: Cell membrane; Single-pass type I membrane protein.; [Isoform 2]: Secreted.; [Soluble interleukin-6 receptor subunit alpha]: Secreted.

Type I cytokine receptor family, Type 3 subfamily

[Isoform 2]: Expressed in peripheral blood mononuclear cells and weakly found in urine and serum. 1%-20% of the total sIL6R in plasma is generated by alternative splicing.

HGNC: 6019

OMIM: 147880

KEGG: hsa:3570

STRING: 9606.ENSP00000357470

UniGene: Hs.135087