본문 바로가기
KERD
논문KCI 등재

IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

초록

Studies over the last 2 decades have identified IL-17 and IL-21 as key cytokines in the modulation of a wide range of immune responses. IL-17 serves as a critical defender against bacterial and fungal pathogens, while maintaining symbiotic relationships with commensal microbiota. However, alterations in its levels can lead to chronic inflammation and autoimmunity. IL-21, on the other hand, bridges the adaptive and innate immune responses, and its imbalance is implicated in autoimmune diseases and cancer, highlighting its important role in both health and disease. Delving into the intricacies of these cytokines not only opens new avenues for understanding the immune system, but also promises innovative advances in the development of therapeutic strategies for numerous diseases. In this review, we will discuss an updated view of the immunobiology and therapeutic potential of IL-17 and IL-21.

Abstract

Studies over the last 2 decades have identified IL-17 and IL-21 as key cytokines in the modulation of a wide range of immune responses. IL-17 serves as a critical defender against bacterial and fungal pathogens, while maintaining symbiotic relationships with commensal microbiota. However, alterations in its levels can lead to chronic inflammation and autoimmunity. IL-21, on the other hand, bridges the adaptive and innate immune responses, and its imbalance is implicated in autoimmune diseases and cancer, highlighting its important role in both health and disease. Delving into the intricacies of these cytokines not only opens new avenues for understanding the immune system, but also promises innovative advances in the development of therapeutic strategies for numerous diseases. In this review, we will discuss an updated view of the immunobiology and therapeutic potential of IL-17 and IL-21.

참고문헌 (159)

  1. Hiam-Galvez KJ, "Systemic immunity in cancer", Nat Rev Cancer, 21, pp.345~359 (2021)
  2. O’Shea JJ, "Cytokines and autoimmunity", Nat Rev Immunol, 2, pp.37~45 (2002)
  3. Mills KH, "IL-17 and IL-17-producing cells in protection versus pathology", Nat Rev Immunol, 23, pp.38~54 (2023)
  4. Akuzum B, "Context-dependent regulation of type17 immunity by microbiota at the intestinal barrier", Immune Netw, 22, pp.e46~ (2022)
  5. Akamatsu N, "Selected IL-21r expression and apoptosis induction by IL-21 in follicular lymphoma", Blood, 104, pp.2284~ (2004)
  6. Ozaki K, "A critical role for IL-21 in regulating immunoglobulin production", Science, 298, pp.1630~1634 (2002)
  7. Brandt K, "Interleukin-21 inhibits dendritic cell activation and maturation", Blood, 102, pp.4090~4098 (2003)
  8. Dong C, "Cytokine regulation and function in T cells", Annu Rev Immunol, 39, pp.51~76 (2021)
  9. McGeachy MJ, "The IL-17 family of cytokines in health and disease", Immunity, 50, pp.892~906 (2019)
  10. Kim BS, "Generation of RORγt+ antigen-specific T regulatory 17 cells from Foxp3 precursors in autoimmunity", Cell Reports, 21, pp.195~207 (2017)
  11. Kim BS, "Type 17 immunity promotes the exhaustion of CD8+ T cells in cancer", J Immunother Cancer, 9, pp.e002603~ (2021)
  12. Veldhoen M, "Interleukin 17 is a chief orchestrator of immunity", Nat Immunol, 18, pp.612~621 (2017)
  13. Shimura E, "Potential role of myeloid cell", eosinophil-derived IL-17 in LPS-induced endotoxin shock, 2014, pp.453, 1~6
  14. Li L, "IL-17 produced by neutrophils regulates IFN-γ-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury", J Clin Invest, 120, pp.331~342 (2010)
  15. Werner JL, "Neutrophils produce interleukin 17A(IL-17A)in a dectin-1-and IL-23-dependent manner during invasive fungal infection", Infect Immun, 79, pp.3966~3977 (2011)
  16. Su Y, "Interleukin-17 receptor D constitutes an alternative receptor for interleukin-17A important in psoriasis-like skin inflammation", Sci Immunol, 4, pp.eaau9657~ (2019)
  17. Huang J, "Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93", Immunity, 54, pp.673~686 (2021)
  18. Ivanov II, "Transcriptional regulation of Th17 cell differentiation", Semin Immunol, 19, pp.409~417 (2007)
  19. Ye P, "Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense", J Exp Med, 194, pp.519~527 (2001)
  20. Chang SH, "Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor", J Biol Chem, 281, pp.35603~35607 (2006)
  21. Qian Y, "The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease", Nat Immunol, 8, pp.247~256 (2007)
  22. Schwandner R, "Requirement of tumor necrosis factor receptor-associated factor(TRAF)6 in interleukin 17 signal transduction", J Exp Med, 191, pp.1233~1240 (2000)
  23. Qu F, "TRAF6-dependent Act1 phosphorylation by the IκB kinase-related kinases suppresses interleukin-17-induced NF-κB activation", Mol Cell Biol, 32, pp.3925~3937 (2012)
  24. Liu C, "Act1, a U-box E3 ubiquitin ligase for IL-17 signaling", Sci Signal, 2, pp.ra63~ (2009)
  25. Li X, "IL-17 receptor-based signaling and implications for disease", Nat Immunol, 20, pp.1594~1602 (2019)
  26. Chong WP, "The cytokine IL-17a limits th17 pathogenicity via a negative feedback loop driven by autocrine induction of IL-24", Immunity, 53, pp.384~397 (2020)
  27. Zhong B, "Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25", Nat Immunol, 13, pp.1110~1117 (2012)
  28. Lee JS, "Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability", Immunity, 43, pp.727~738 (2015)
  29. Conti HR, "Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis", J Exp Med, 206, pp.299~311 (2009)
  30. Liang SC, "Interleukin(IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides", J Exp Med, 203, pp.2271~2279 (2006)
  31. Conti HR, "IL-17 receptor signaling in oral epithelial cells is critical for protection against oropharyngeal candidiasis", Cell Host Microbe, 20, pp.606~617 (2016)
  32. Cho JS, "IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice", J Clin Invest, 120, pp.1762~1773 (2010)
  33. Chen X, "IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells", J Exp Med, 216, pp.195~214 (2019)
  34. Lai Y, "The antimicrobial protein REG3A regulates keratinocyte proliferation and differentiation after skin injury", Immunity, 37, pp.74~84 (2012)
  35. Krstić J, "Urokinase type plasminogen activator mediates interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration", Biochim Biophys Acta, 1853, pp.431~444 (2015)
  36. Ozaki K, "Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain", Proc Natl Acad Sci U S A, 97, pp.11439~11444 (2000)
  37. Wei L, "IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner", J Biol Chem, 282, pp.34605~34610 (2007)
  38. Suto A, "Development and characterization of IL-21-producing CD4+ T cells", J Exp Med, 205, pp.1369~1379 (2008)
  39. Lee GR, "Molecular mechanisms of t helper cell differentiation and functional specialization", Immune Netw, 23, pp.e4~ (2023)
  40. Coquet JM, "IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production", J Immunol, 178, pp.2827~2834 (2007)
  41. Bae EA, "Roles of NKT cells in cancer immunotherapy", Arch Pharm Res, 42, pp.543~548 (2019)
  42. Spolski R, "IL-21 and T follicular helper cells", Int Immunol, 22, pp.7~12 (2010)
  43. Nurieva RI, "Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages", Immunity, 29, pp.138~149 (2008)
  44. Vogelzang A, "A fundamental role for interleukin-21 in the generation of T follicular helper cells", Immunity, 29, pp.127~137 (2008)
  45. Bryant VL, "Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells : predominant role of IL-21 produced by CXCR5+ T follicular helper cells", J Immunol, 179, pp.8180~8190 (2007)
  46. Ming S, "GITR promotes the polarization of TFH-like cells in helicobacter pylori-positive gastritis", Front Immunol, 12, pp.736269~ (2021)
  47. Koh CH, "GITR agonism triggers antitumor immune responses through IL21-expressing follicular helper T cells", Cancer Immunol Res, 8, pp.698~709 (2020)
  48. Oja AE, "GITR shapes humoral immunity by controlling the balance between follicular T helper cells and regulatory T follicular cells", Immunol Lett, 222, pp.73~79 (2020)
  49. Jin H, "Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis", J Immunol, 173, pp.657~665 (2004)
  50. Spolski R, "Interleukin-21 : basic biology and implications for cancer and autoimmunity", Annu Rev Immunol, 26, pp.57~79 (2008)
  51. Wan CK, "Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells", Proc Natl Acad Sci U S A, 112, pp.9394~9399 (2015)
  52. Solaymani-Mohammadi S, "Regulation of intestinal epithelial cell cytoskeletal remodeling by cellular immunity following gut infection", Mucosal Immunol, 6, pp.369~378 (2013)
  53. Strengell M, "IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response", J Immunol, 169, pp.3600~3605 (2002)
  54. Spolski R, "Interleukin-21 : a double-edged sword with therapeutic potential", Nat Rev Drug Discov, 13, pp.379~395 (2014)
  55. Kwon H, "Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors", Immunity, 31, pp.941~952 (2009)
  56. Li P, "BATF-JUN is critical for IRF4-mediated transcription in T cells", Nature, 490, pp.543~546 (2012)
  57. Ciofani M, "A validated regulatory network for Th17 cell specification", Cell, 151, pp.289~303 (2012)
  58. Glasmacher E, "A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes", Science, 338, pp.975~980 (2012)
  59. Seo H, "BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells", Nat Immunol, 22, pp.983~995 (2021)
  60. Distler JH, "Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis", Arthritis Rheum, 52, pp.856~864 (2005)
  61. Caruso R, "IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis", J Immunol, 178, pp.5957~5965 (2007)
  62. Crotty S, "Follicular helper CD4 T cells(TFH)", Annu Rev Immunol, 29, pp.621~663 (2011)
  63. Yang L, "IL-21 and TGF-beta are required for differentiation of human T(H)17 cells", Nature, 454, pp.350~352 (2008)
  64. Zhou L, "IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways", Nat Immunol, 8, pp.967~974 (2007)
  65. Nurieva R, "Essential autocrine regulation by IL-21 in the generation of inflammatory T cells", Nature, 448, pp.480~483 (2007)
  66. Brüstle A, "The development of inflammatory TH-17 cells requires interferon-regulatory factor 4", Nat Immunol, 8, pp.958~966 (2007)
  67. Chen Q, "IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor", Immunity, 29, pp.899~911 (2008)
  68. Nurieva RI, "Bcl6 mediates the development of T follicular helper cells", Science, 325, pp.1001~1005 (2009)
  69. Yu D, "The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment", Immunity, 31, pp.457~468 (2009)
  70. Yu J, "Interleukin-21 promotes the development of ulcerative colitis and regulates the proliferation and secretion of follicular T helper cells in the colitides microenvironment", Mol Med Rep, 11, pp.1049~1056 (2015)
  71. Gassen RB, "IL-21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection", Immunol Cell Biol, 99, pp.309~322 (2021)
  72. Strengell M, "IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells", J Immunol, 170, pp.5464~5469 (2003)
  73. Monteleone G, "Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease", Gastroenterology, 128, pp.687~694 (2005)
  74. Zeng R, "Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function", J Exp Med, 201, pp.139~148 (2005)
  75. Casey KA, "IL-21 promotes differentiation of naive CD8 T cells to a unique effector phenotype", J Immunol, 178, pp.7640~7648 (2007)
  76. Hinrichs CS, "IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy", Blood, 111, pp.5326~5333 (2008)
  77. Zander R, "Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection", Immunity, 55, pp.475~493 (2022)
  78. Rankin AL, "IL-21 receptor is critical for the development of memory B cell responses", J Immunol, 186, pp.667~674 (2011)
  79. Rankin AL, "IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL", MpJ-Fas(lpr, J mice, pp.J Immunol, 2012[DOI]
  80. Pène J, "Cutting edge : IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells", J Immunol, 172, pp.5154~5157 (2004)
  81. Avery DT, "IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4", J Immunol, 181, pp.1767~1779 (2008)
  82. Ettinger R, "The role of IL-21 in regulating B-cell function in health and disease", Immunol Rev, 223, pp.60~86 (2008)
  83. Ozaki K, "Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6", J Immunol, 173, pp.5361~5371 (2004)
  84. Konforte D, "IL-21 : an executor of B cell fate", J Immunol, 182, pp.1781~1787 (2009)
  85. Linterman MA, "IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses", J Exp Med, 207, pp.353~363 (2010)
  86. Gonzalez DG, "Nonredundant roles of IL-21 AND IL-4 in the phased initiation of germinal center B cells and subsequent self-renewal transitions", J Immunol, 201, pp.3569~3579 (2018)
  87. Avery DT, "STAT3 is required for IL-21-induced secretion of IgE from human naive B cells", Blood, 112, pp.1784~1793 (2008)
  88. Berglund LJ, "IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts", Blood, 122, pp.3940~3950 (2013)
  89. Korn T, "IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells", Nature, 448, pp.484~487 (2007)
  90. Attridge K, "IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis", Blood, 119, pp.4656~4664 (2012)
  91. Huber M, "IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype", Proc Natl Acad Sci U S A, 105, pp.20846~20851 (2008)
  92. Piao WH, "IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis", Scand J Immunol, 67, pp.37~46 (2008)
  93. Pot C, "Cutting edge : IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells", J Immunol, 183, pp.797~801 (2009)
  94. Spolski R, "IL-21 mediates suppressive effects via its induction of IL-10", J Immunol, 182, pp.2859~2867 (2009)
  95. Kasaian MT, "IL-21 limits NK cell responses and promotes antigen-specific T cell activation : a mediator of the transition from innate to adaptive immunity", Immunity, 16, pp.559~569 (2002)
  96. Skak K, "Interleukin-21 activates human natural killer cells and modulates their surface receptor expression", Immunology, 123, pp.575~583 (2008)
  97. Seo H, "IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours", Nat Commun, 8, pp.15776~ (2017)
  98. Yano M, "IL-21-expanded natural killer cells as autologous cell therapy for cll", Blood, 134, pp.4302~ (2019)
  99. Strengell M, "IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells", J Leukoc Biol, 79, pp.1279~1285 (2006)
  100. Wan CK, "The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells", Immunity, 38, pp.514~527 (2013)
  101. De Nitto D, "Interleukin-21 triggers effector cell responses in the gut", World J Gastroenterol, 16, pp.3638~3641 (2010)
  102. van Heel DA, "A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21", Nat Genet, 39, pp.827~829 (2007)
  103. Asano K, "Molecular scanning of interleukin-21 gene and genetic susceptibility to type 1 diabetes", Hum Immunol, 68, pp.384~391 (2007)
  104. Teixeira VH, "Testing for the association of the KIAA1109", Tenr, IL21 gene region with rheumatoid arthritis in a European family-based study, pp.Arthritis Res Ther, 2009[DOI]
  105. Costanzo A, "IL-21 in the pathogenesis and treatment of skin diseases", J Dermatol Sci, 60, pp.61~66 (2010)
  106. Park Y, "Recent advances in cell therapeutics for systemic autoimmune diseases", Immune Netw, 22, pp.e10~ (2022)
  107. Matusevicius D, "Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis", Mult Scler, 5, pp.101~104 (1999)
  108. Komiyama Y, "IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis", J Immunol, 177, pp.566~573 (2006)
  109. Tzartos JS, "Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis", Am J Pathol, 172, pp.146~155 (2008)
  110. Kotake S, "IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis", J Clin Invest, 103, pp.1345~1352 (1999)
  111. Ziolkowska M, "High levels of IL-17 in rheumatoid arthritis patients : IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism", J Immunol, 164, pp.2832~2838 (2000)
  112. Sato K, "Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction", J Exp Med, 203, pp.2673~2682 (2006)
  113. Nakae S, "Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice", J Immunol, 171, pp.6173~6177 (2003)
  114. Wong CK, "Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus : implications for Th17-mediated inflammation in auto-immunity", Clin Immunol, 127, pp.385~393 (2008)
  115. Johansen C, "Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin", Br J Dermatol, 160, pp.319~324 (2009)
  116. Schüler R, "Antagonization of IL-17a attenuates skin inflammation and vascular dysfunction in mouse models of psoriasis", J Invest Dermatol, 139, pp.638~647 (2019)
  117. Stolfi C, "Involvement of interleukin-21 in the regulation of colitis-associated colon cancer", J Exp Med, 208, pp.2279~2290 (2011)
  118. Gensous N, "T follicular helper cells in autoimmune disorders", Front Immunol, 9, pp.1637~ (2018)
  119. Wang S, "IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE", Nat Commun, 9, pp.1758~ (2018)
  120. Wang Y, "IL-21", IL-21R signaling suppresses intestinal inflammation induced by DSS through regulation of Th responses in lamina propria in mice, 2016, pp.6, 31881~
  121. Fina D, "Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease", Gut, 57, pp.887~892 (2008)
  122. Caruso R, "Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis", Nat Med, 15, pp.1013~1015 (2009)
  123. Wang Y, "Interleukin-21 is associated with the severity of psoriasis vulgaris through promoting CD4+ T cells to differentiate into Th17 cells", Am J Transl Res, 8, pp.3188~3196 (2016)
  124. Shi Y, "IL-21 induces an imbalance of Th17", Treg cells in moderate-to-severe plaque psoriasis patients, 2019, pp.10, 1865~
  125. Dolff S, "Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus", Arthritis Res Ther, 13, pp.R157~ (2011)
  126. Coffelt SB, "IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis", Nature, 522, pp.345~348 (2015)
  127. Wu P, "γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer", Immunity, 40, pp.785~800 (2014)
  128. Ma S, "IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma", Cancer Res, 74, pp.1969~1982 (2014)
  129. Zhuang Y, "CD8+ T cells that produce interleukin-17 regulate myeloid-derived suppressor cells and are associated with survival time of patients with gastric cancer", Gastroenterology, 143, pp.951~962 (2012)
  130. Chung L, "Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells(vol 23, pg 203, 2018)", Cell Host Microbe, 23, pp.421~421 (2018)
  131. Chang SH, "T helper 17 cells play a critical pathogenic role in lung cancer", Proc Natl Acad Sci U S A, 111, pp.5664~5669 (2014)
  132. Jin C, "Commensal microbiota promote lung cancer development via gamma delta T cells", Cell, 176, pp.998~1013 (2019)
  133. Takeuchi A, "IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer", Eur J Immunol, 41, pp.246~251 (2011)
  134. Chen CL, "IL-17 induces antitumor immunity by promoting beneficial neutrophil recruitment and activation in esophageal squamous cell carcinoma", OncoImmunology, 7, pp.e1373234~ (2018)
  135. Deng S, "Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3-CD8+ T cells", JCI Insight, 5, pp.e132000~ (2020)
  136. Topchyan P, "Harnessing the IL-21-batf pathway in the CD8+ T cell anti-tumor response", Cancers(Basel), 13, pp.1263~ (2021)
  137. Wang G, "In vivo antitumor activity of interleukin 21 mediated by natural killer cells", Cancer Res, 63, pp.9016~9022 (2003)
  138. Takaki R, "IL-21 enhances tumor rejection through a NKG2D-dependent mechanism", J Immunol, 175, pp.2167~2173 (2005)
  139. Gowda A, "IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro", Blood, 111, pp.4723~4730 (2008)
  140. de Totero D, "The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK", STAT and ERK1, Blood, pp.2008, 111[DOI]
  141. Akamatsu N, "High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma", Cancer Lett, 256, pp.196~206 (2007)
  142. Sarosiek KA, "Interleukin-21-induced apoptosis and cell death of diffuse large B-cell lymphoma(DLBCL)cell lines and primary tumors are associated with an induction of bim", Blood, 108, pp.2503~ (2006)
  143. Sarosiek KA, "Interleukin-21 induces cell cycle arrest and apoptosis of diffuse large b-cell lymphomas(DLBCL)via activation of stat3 and upregulation of c-myc", Blood, 112, pp.225~225 (2008)
  144. Jung SM, "Targeted immunotherapy for autoimmune disease", Immune Netw, 22, pp.e9~ (2022)
  145. Yin Y, "Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis : a systematic review and meta-analysis", Arthritis Res Ther, 22, pp.111~ (2020)
  146. Drakos A, "A review of the clinical trial landscape in psoriasis : an update for clinicians", Dermatol Ther(Heidelb), 12, pp.2715~2730 (2022)
  147. Almassian B, "Carg-2020, an oncolytic artificial virus co-delivering three immunomodulators, to regress and cure established tumors in mice", J Clin Oncol, 39, pp.e14560~ (2021)
  148. Denis A, "The 2023 pipeline of disease-modifying antirheumatic drugs(DMARDs)in clinical development for spondyloarthritis(including psoriatic arthritis) : a systematic review of trials", RMD Open, 9, pp.e003279~ (2023)
  149. Nasonov E, "Developments of Russian original biological agents for the treatment of immunoinflammatory rheumatic diseases", Rheumatol Sci Pract, 55, pp.201~210 (2017)
  150. Nie S, "Biology drives the discovery of bispecific antibodies as innovative therapeutics", Antib Ther, 3, pp.18~62 (2020)
  151. Mullard A, "Bispecific antibody pipeline moves beyond oncology", Nat Rev Drug Discov, 16, pp.666~668 (2017)
  152. Hua F, "Anti-IL21 receptor monoclonal antibody(ATR-107) : safety, pharmacokinetics, and pharmacodynamic evaluation in healthy volunteers : a phase I, first-in-human study", J Clin Pharmacol, 54, pp.14~22 (2014)
  153. Danese S, "The future of drug development for inflammatory bowel disease : the need to ACT(advanced combination treatment)", Gut, 71, pp.2380~2387 (2022)
  154. Zhang R, "Novel oncolytic virus armed with interleukin-21 enhances immune oncotherapy", Cancer Res, 79, pp.1462~1462 (2019)
  155. Zhu Z, "Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways", Mol Cancer, 21, pp.196~ (2022)
  156. Leonard WJ, "Strategies to therapeutically modulate cytokine action", Nat Rev Drug Discov, 22, pp.827~854 (2023)
  157. Sullivan JM, "Generation of IL-21 INDUKINETM molecules for the treatment of cancer", Cancer Res, 83, pp.1829~1829 (2023)
  158. Milovanovic J, "Interleukin-17 in chronic inflammatory neurological diseases", Front Immunol, 11, pp.947~ (2020)
  159. Leonard WJ, "IL-21 signaling in immunity", F1000 Res, 5, pp.F1000~ (2016)

관련 논문AI추천

이 간행물의 다른 논문 (9건)