Inflammation Research

, Volume 63, Issue 11, pp 943–950 | Cite as

Elevated levels of Th17 cells and Th17-related cytokines are associated with disease activity in patients with inflammatory bowel disease

  • Wenyu Jiang
  • Jiewen Su
  • Xiaofei Zhang
  • Xiuqin Cheng
  • Jun Zhou
  • Ruihua Shi
  • Hongjie Zhang
Original Research Paper



Interleukin-17(IL-17)-producing T helper(Th)17 cells are considered as a new subset of cells critical to the development of inflammatory bowel disease (IBD). We aimed to investigate the distribution of Th17 cells, the expressions of Th17-related cytokines (IL-17, IL-21 and IL-22) and their association with disease activity in IBD patients.


We collected intestinal tissue biopsies from 40 patients with active ulcerative colitis (UC), 20 patients with active Crohn’s disease (CD) and 20 healthy controls. The distribution of Th17 cells and expressions of Th17-related cytokines in colonic tissues were evaluated by a standard immunohistochemical procedure. Serum IL-17, IL-21 and IL-22 levels were determined by ELISA. Pearson’s and Spearman’s correlation analyses were performed to analyze the correlation between the number of Th17 cells, the expressions of Th17-related cytokines and disease activity index, endoscopic and histological grading, and CRP and PLT levels, respectively.


Compared with healthy controls, the number of Th17 cells and the expressions of IL-17, IL-21 and IL-22 were significantly increased in active IBD patients (P < 0.05). In addition, Pearson’s and Spearman’s correlation analyses showed that the number of Th17 cells and the expressions of Th17-related cytokines were correlated with disease activity index, endoscopic and histological grading, CRP and PLT levels (P < 0.05).


Th17 cells and Th17-related cytokines (IL-17, IL-21 and IL-22) were increased in the intestinal mucosa in active IBD patients and may play an important role in disease activity and mucosal damage.


Inflammatory bowel disease (IBD) Ulcerative colitis (UC) Crohn’s disease (CD) Th17 Cells IL-17 IL-21 IL-22 



This work was supported by grants from the National Natural Science Foundation of China (No. 81270469) and the Key Medical Personnel of Jiangsu Province (No. RC2011063).


  1. 1.
    Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573–621.PubMedCrossRefGoogle Scholar
  2. 2.
    Abraham Clara, Medzhitov Ruslan. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 2011;140:1729–37.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Fuss IJ. Is the Th1/Th2 paradigm of immune regulation applicable to IBD? Inflamm Bowel Dis. 2008;14(Suppl. 2):S110–2.PubMedCrossRefGoogle Scholar
  4. 4.
    Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Fantini MC, Monteleone G, MacDonald TT. IL-21 comes of age as a regulator of effector T cells in the gut. Mucosal Immunol. 2008;1(2):110–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Andoh A, Zhang Z, Inatomi O, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology. 2005;129:969–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Bernstein CN, Fried M, Krabshuis JH, et al. World Gastroenterology Organization Practice Guidelines for the Diagnosis and Management of IBD in 2010. Inflamm Bowel Dis. 2010;16:112–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Daperno M, D’ Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for disease: the SES-CD. Gastrointest Endosc. 2004;60:505–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Tsai YS, Jou YC, Lee GF, Chen YC, Shiau AL, et al. Aberrant prothymosin-alpha expression in human bladder cancer. Urology. 2009;73:188–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Ryu JW, Lee JH, Choi YH, Lee YT, Choi BT. Effects of protein phosphatase inhibitors on the phosphorylation of spinal cord N-methyl-D-aspartate receptors following electroacupuncture stimulation in rats. Brain Res Bull. 2008;75:687–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Raza A, Yousaf W, Giannella R, et al. Th17 cells: interactions with predisposing factors in the immunopathogenesis of inflammatory bowel disease. Expert Rev Clin Immunol. 2012;8(2):161–8.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Niu Q, Cai B, Huang ZC, et al. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2011 Aug 2. [Epub ahead of print].Google Scholar
  13. 13.
    Becher B. Segal BM.T(H)17 cytokines in autoimmune neuro-inflammation. Curr Opin Immunol. 2011;23(6):707–12.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Eastaff-Leung N, Mabarrack N, Barbour A, et al. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol. 2010;30(1):80–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Holtta Veera, Klemetti Paula, Salo Harri M, et al. Interleukin-17 immunity in pediatric Crohn disease and ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013;57(3):287–92.PubMedCrossRefGoogle Scholar
  16. 16.
    Laan M, Lo¨tvall J, Chung KF, et al. IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. Br J Pharmacol. 2001;133:200–6.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Awane M, Andres PG, Li DJ, et al. NF-kappa B-inducing kinase is a common mediator of IL-17-, TNFalpha-, and IL-1beta-induced chemokine promoter activation in intestinal epithelial cells. J Immunol. 1999;162:5337–44.PubMedGoogle Scholar
  18. 18.
    Kolls JK, Linden A. IL-17 family members and inflammation. Immunity. 2004;21:467–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Curtis MM, Way SS. Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens. Immunology. 2009;126:177–85.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Bai A, Lu N, Guo Y, et al. All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg/Th17 profile in human ulcerative and murine colitis. J Leukoc Biol. 2009;86(4):959–69.PubMedCrossRefGoogle Scholar
  21. 21.
    Yamamoto-Furusho JK, Miranda-Pérez E, Fonseca-Camarillo G, et al. Interleukin 21 expression is increased in rectal biopsies from patients with ulcerative colitis. Inflamm Bowel Dis. 2010;16(7):1090.PubMedCrossRefGoogle Scholar
  22. 22.
    Strengell M, Sareneva T, Foster D, et al. IL-21 up-regulates the expression of gene associated with innate immunity and Th1 response. J Immunol. 2002;169:3600–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Spolski R, Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 2008;26:57–79.PubMedCrossRefGoogle Scholar
  24. 24.
    Qi W, Huang X, Wang J. Correlation between Th17 cells and tumor microenvironment. Cell Immunol. 2013;285(1–2):18–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Zenewicz LA, Flavell RA. Recent advances in IL-22 biology. Int Immunol. 2011;23(3):159–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Solem CA, Loftus EV Jr, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:707–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Cabrera-Abreu JC, Davies P, Matek Z, Murphy MS. Performance of blood tests in diagnosis of inflammatory bowel disease in a specialist clinic. Arch Dis Child. 2004;89(1):69–71.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Wenyu Jiang
    • 1
    • 2
  • Jiewen Su
    • 1
  • Xiaofei Zhang
    • 1
  • Xiuqin Cheng
    • 1
  • Jun Zhou
    • 1
  • Ruihua Shi
    • 1
  • Hongjie Zhang
    • 1
  1. 1.Department of GastroenterologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of GastroenterologyThe Second People’s Hospital of WuxiWuxiChina

Personalised recommendations