Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells. Implicated in the generation and maintenance of T follicular helper (Tfh) cells and the formation of germinal-centers. Together with IL6, control the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection. May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.

1. There was negative correlation between the expression of IL12 and miR21 in the serum of patients with acute myeloid leukemia. PMID: 30106099
2. IL-21 can potently induce CD11c(hi)T-bet(+) B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells PMID: 29717110
3. IL-21 enhances cartilage inflammation to promote cartilage degradation through the JAK-STAT signaling pathway in the cartilage of Osteonecrosis of Femoral Head patients. PMID: 29247327
4. SHP-2 may augment the ERK1/2 activity and cell proliferation activity in IL-21 signaling. PMID: 29503347
5. this study shows that Th9 cells promote antitumor immunity via IL-21 PMID: 28918288
6. AD patients, especially those with acute lesions, exhibited elevated serum IL-21 levels. Therefore, IL-21 might be associated with the acute aggravation of AD. PMID: 27884624
7. Study shows that IL-21 levels were non-specifically elevated across all febrile children, irrespective of Kawasaki disease diagnosis. PMID: 28427414
8. These results suggest that cetuximab treatment in combination with IL-21 adjuvant therapy in patients with EGFR-positive pancreatic cancer results in significant NK cell activation, irrespective of KRAS mutation status, and may be a potential therapeutic strategy PMID: 27435400
9. serum IL-21 levels at 12 weeks treatment was significantly elevated, which can predict the EVR, and contributes to individualization of antiviral therapy in HBeAg-positive CHB+NAFLD patients. PMID: 26840345
10. IL-23 activates gammadelta T cells in early stage PNS, which amplifies the Th17 cell population and leads to kidney injury through the secretion of IL-21. PMID: 29119640
11. IL-21 promotes the survival and CTLA-4 expression of Tregs and enhanced the suppressive capacity of Tregs during HIV infection. These results broaden the understanding of HIV pathogenesis and provide critical information for HIV interventions. PMID: 28043029
12. IL-21 are important in the pathophysiology of chronic rhinosinusitis with nasal polyposis PMID: 29131072
13. Data show that interleukin-21-primed cytotoxic T-cell lymphocytes (CTL) with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade is safe and produces durable clinical responses. PMID: 27269940
14. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC. PMID: 28887120
15. IL-21 modulates the effector functions of T, B and NK cells, which not only have key roles in antitumoral and antiviral immunity but also in exerting major effects on inflammatory responses promoting the development of autoimmune diseases. PMID: 26748727
16. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells. PMID: 27157859
17. Report efficient retroviral vector transduction of primary human natural killer cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21 for cancer immunotherapy. PMID: 28802832
18. IL21 reduction in osteosarcoma patients due to PD-1 and pd-L1 mediated follicular helper T cells suppression. PMID: 28650673
19. this study shows that induction of IL-21 in T follicular helper cells is an indicator of influenza vaccine response in a HIV-infected pediatric cohort PMID: 28130496
20. IL-21 levels in rheumatoid arthritis synovial fluid were associated with matrix metalloproteinase (MMP)-1 and MMP-3. PMID: 27733582
21. the elevated level of IL-2+ and IL-21+ T cells and a positive correlation between IL-21+ cells with clinical activity index in ulcerative colitis patients may contribute to the pathogenesis of disease. PMID: 28685527
22. these results demonstrate a novel function for IL-21 in tuning NK and CD4+ T cell interactions promoting a specific expansion of central memory lymphocytes PMID: 27233967
23. Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient PMID: 27242164
24. Our work suggests that IL-21 regulates megakaryocyte development and platelet homeostasis. Thus, IL-21 may link immune responses to physiological or pathological platelet-dependent processes. PMID: 28057742
25. expression significantly downregulated in skin and blood of patients with tumor mycosis fungoides PMID: 26825047
26. this study shows that Th17/Treg imbalance and increased IL-21 are associated with liver injury in patients with chronic HBV infection PMID: 28259000
27. The findings of the current study indicate an association between IL-21+TFH cells and disease activity. IL-21+TFH levels may prove to be a useful marker of disease activity in OA patients. PMID: 28112376
28. IL-21 is involved in the pathological development of Intervertebral Disc Degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-alpha through the STAT signaling pathway PMID: 28233079
29. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL-21 gene are associated with the susceptibility of HBV-related hepatocellular carcinoma (HCC) and chronic HBV infection. The genetic variant may in fact cause protection against the HBV-related HCC. PMID: 27122304
30. Hepatitis C virus specific IL-21 producing T cells but not IL-17A producing T Cells are associated with hepatitis C viral control in HIV/ hepatitis C virus coinfection. PMID: 27124305
31. this study shows that the serum levels of IL-21 are higher in Iranian diabetes type I patients compared to the healthy individuals PMID: 27611173
32. We characterized the expressed IL-21 gene from immune tissues of two macropod species, the tammar wallaby (Macropus eugenii), a model macropod, and the closely related endangered bridled nailtail wallaby (Onychogalea fraenata). The open reading frame of macropod IL-21 is 462 nucleotides in length and encodes a 153-mer putative protein that has 46% identity with human IL-21. PMID: 27306193
33. The rs2055979 C>A polymorphism of the IL-21 gene is associated with cryptorchidism susceptibility, and the C allele increases the risk of cryptorchidism in a Chinese Han population. PMID: 26990619
34. Polymorphisms in IL21 may be associated with sepsis risk PMID: 27295539
35. review on IL-21 as is a crucial cytokine associated with pemphigus PMID: 26945832
36. There is a strong association between IL2/IL21 rs6822844 variant and susceptibility to rheumatoid arthritis (RA) in the Algerian population; this association is independent from the autoantibodies status of RA patients. PMID: 26917059
37. HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21. PMID: 26818544
38. IL-21 exerts major effects on B-cell activation and differentiation or apoptosis during humoral immune responses, and also affects different subtypes of T cells. (Review) PMID: 26466984
39. The results suggest that IL-21 promotes migration and invasion of Rheumatoid arthritis-Fibroblast-like synoviocytes. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of Rheumatoid arthritis. PMID: 26646950
40. IL-12 induced the generation of IL-21- and IFN-gamma-co-expressing poly-functional CD4+ T cells from human naive CD4+ T cells. PMID: 26566861
41. IL-21 expression is promoted by MEKK4 in malignant T cells and is associated with progression risk in cutaneous T-cell lymphoma PMID: 26802931
42. Human IL-21+IFN-gamma+CD4+ T cells in nasal polyps are regulated by IL-12. PMID: 26239551
43. CD3(+)TCRvbeta11(+) NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection. PMID: 26416419
44. IL-21 protein was higher in serum and mRNA and protein were higher in disc tissue of patients with lumbar disc herniation compared to controls. PMID: 26742440
45. both IL-21 rs907715 and rs2221903 polymorphisms may be associated with systemic lupus erythematosus susceptibility (meta-analysis) PMID: 26345892
46. all Ifng+ T cells produced IL-21, but only a small percentage of highly proliferative Ifng+ T cells maintained a T-bethi phenotype PMID: 26646149
47. increased production in patients with more severe systemic lupus erythematosus PMID: 26358223
48. the minor allele T of both rs6822844 (T vs G, OR = 0.72, 95%CI = 0.67-0.78, P < 0.001) and rs6840978 (T vs C, OR = 0.76, 95%CI = 0.71-0.83, P < 0.001) in IL21 significantly decreased the risk of celiac disease (Meta-Analysis) PMID: 26535636
49. the ability of IL21 to modulate gene and miRNA expressions in CD40-activated Chronic Lymphocytic Leukemiacells, was studied. PMID: 26305332
50. Loss of IL-21 is considered to lead to atrophied germinal centers in multicentric Castleman's disease. PMID: 26377996

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Secreted.

IL-15/IL-21 family

Expressed in activated CD4-positive T-cells but not in CD8-positive T-cells, B-cells, or monocytes.

HGNC: 6005

OMIM: 605384

KEGG: hsa:59067

STRING: 9606.ENSP00000264497

UniGene: Hs.567559