Original Article
  

Different Doses of Transforming Growth Factor-β on In vitro Differentiation of Human Naïve CD4+ T Cells to T Helper 17

Abstract

An appropriate differentiation of distinct human CD4+ T cell subset is critical for manipulating these cells for using in immunity related diseases. Despite various attempts to clarify the role of different factors involved in Th17 differentiation, many crucial contradictions yet remained to be optimized. Although it has been shown that the differentiation of in-vitro Th17 cells culture conditions requires the presence of IL-1beta, IL-23, IL-2, IL-21, IL-6 and TGF-β, the optimum amount of TGF-β regulating in vitro human Th17 cell differentiation is still unclear. In the current study, a flow cytometric assay was used to evaluate the effect of different concentrations of TGF-β and a combination of IL-1beta, IL-23, IL-2 without using IL-6 on development of Interleukin (IL)-17–producing T helper (Th17) cells. According to our findings, 0.1 ng/ml of TGF-β significantly increases the expression of IL-17 in comparison to other concentrations of this cytokine. Results indicated the vital role of TGF-β cytokine in the polarization of human Th17 cells in vitro.

1. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136(7):2348-57.

2. Killar L, MacDonald G, West J, Woods A, Bottomly K.Cloned, Ia-restricted T cells that do not produce interleukin 4 (IL 4)/B cell stimulatory factor 1 (BSF-1) fail to help antigen-specific B cells. J Immunol 1987;138(6):1674-9.

3. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature. 1996; 383(6603):787-93.

4. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity 2008; 28(4):445-53.

5. Chen Z, Tato CM, Muul L, Laurence A, O'Shea JJ.Distinct regulation of interleukin‐17 in human T helper lymphocytes. Arthritis Rheum 2007; 56(9):2936-46.

6. Waite JC, Skokos D. Th17 response and inflammatory autoimmune diseases. Int J Inflam 2012; 2012:819467.

7. Chen DY, Chen YM, Lan JL, Lin CC, Chen HH, Hsieh CW. Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease. Rheumatology (Oxford, England) 2010; 49(12):2305-12.

8. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007; 8(4):345-50.

9. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441(7090):235-8.

10. Veldhoen M, Hocking RJ, Flavell RA, Stockinger B.Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 2006;7(11):1151-6.

11. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells. Semin Immunol 2007; 8(9):942-9.

12. Ivanov II, Zhou L, Littman DR. Transcriptional regulation of Th17 cell differentiation. Semin Immunol 2007; 19(6):409-17.

13. Manel N, Unutmaz D, Littman DR. The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Semin Immunol 2008; 9(6):641-9.

14. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, et al. IL-21 and TGF-&bgr; are required for differentiation of human TH17 cells. Nature 2008; 454(7202):350-2.

15. Ghoreschi K, Laurence A, Yang X-P, Tato CM, McGeachy MJ, Konkel JE, et al. Generation of pathogenic TH17 cells in the absence of TGF-[bgr] signalling. Nature 2010; 467(7318):967-71.

16. Hatton RD. TGF-beta in Th17 cell development: the truth is out there. Immunity 2011; 34(3):288-90.

17. Stockinger B, Veldhoen M. Differentiation and function of Th17 T cells. Curr Opin Immunol 2007; 19(3):281-6.

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IssueVol 14, No 6 (2015) QRcode
SectionOriginal Article(s)
Keywords
CD4 T cells Th17 cells Transforming growth factor-β
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How to Cite
1.
Ghaedi M, Namdari H, Rahimzadeh P, Morteza Gholi S, Azimi Mohamadabadi M, Salehi E. Different Doses of Transforming Growth Factor-β on In vitro Differentiation of Human Naïve CD4+ T Cells to T Helper 17. Iran J Allergy Asthma Immunol. 2015;14(6):633-637.