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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 5  |  Page : 954-956
Th-17 Lymphocytes


London NW1 8JS, United Kingdom

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Date of Web Publication31-Aug-2010
 

How to cite this article:
Wardle E N. Th-17 Lymphocytes. Saudi J Kidney Dis Transpl 2010;21:954-6

How to cite this URL:
Wardle E N. Th-17 Lymphocytes. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Dec 8];21:954-6. Available from: http://www.sjkdt.org/text.asp?2010/21/5/954/68902
To the Editor,

We know that there are Th-1 (T helper type 1) CD4+ T effector lymphocytes, which combat infections by intracellular pathogens via forma­tion of the cytokines Il-2 and IFNy (interferon­gamma), and conversely there are Th-2 CD4+T cells, which help the clearance of helminths and parasites by producing the interleukins Il­4,Il-5, and Il-13. [1] The nephrologist may be in­terested because Th-1 cells feature in glome­rulonephritides such as IgA nephropathy and lupus nephritis. [2],[3] Th-2 lymphocytes and their cytokines Il- 4 and Il-13 were demonstrated to decrease the trans-epithelial electrical resis­tance of rat glomerular visceral epithelial cells, so causing proteinuria. [4]

In recent years, Th17 CD4+T cells have been described. [5] Perhaps surprisingly, γδ T cells are a major source of Il-17 but so are the CD4+ and CD8+ T cells. [6] Th17 cells produce Il-17 and defend against extracellular bacteria and fungi, especially at epithelial cell surfaces. [7] Indeed, they can produce the anti-microbial peptide β-defensin 2. Therefore, they deal with pathogens like Klebsiella pneumoniae and Can­dida albicans in addition to intracellular bac­teria like Listeria monocytogenes,  Salmonella More Details enterica, and Mycobacterium tuberculosis. In particular, Il-17 promotes the early recruitment of neutrophils to an inflammatory site. At first sight a nephrologist may not be impressed, but Th17 cells have been found in the kidneys in SLE nephritis. [8] Remarkably in SLE there are double negative CD4-CD8- T lymphocytes in the blood and kidneys, which produce Il-17. Is it then possible that Th17 cells will be found in other forms of glomerulonephritis? Some functions formerly attributed to Th1 cells could be mediated by these distinct Th-17 cells! Well, since dendritic cells within kidneys are an early source of proinflammatory mediators,one might expect generation of Th17 cells in a variety of circumstances. When unilateral ureteric obs­truction was created in CB57BL/6 mice, Dong et al. [9] could demonstrate production of Il-17 secreting CD4 memory cells. Without doubt, Th17 cells are involved in cardiac allograft re­jection, [10] which lends support to the suppo­sition that they must be involved in renal allo­graft rejection, [11] albeit rejection is a Th-1 reac­tion and to date their role has not been de­fined! Cook and Pusey at Hammersmith using Il-17 knock-outs found that Il-17 plays a role in accelerated nephrotoxic nephritis in mice. [12] Furthermore Salama and Pusey recorded that serum Il-17 and Il-23 levels are elevated in patients with ANCA associated vasculitis. [13]

There has been a recent review of Th-17 cell derived cytokines. [14] One can be interested in the roles of Il-17A and Il-17F, and the parts played by Il-21 and Il-22, and Il-26.The seve­ral roles of each of these cytokines are being investigated. Th17 cells feature on epithelial/ mucosal cell surfaces, so what are they some­times doing within kidneys and how Th17 cells become involved in autoimmunity are still being explored.

Pathways specific transcription factors are ne­cessary for the development of the different forms of T helper lymphocytes. Nuclear RORγt is necessary for Th-17 cells, as is RORα in mice [Figure 1]. [15],[16],[17]
Figure 1 :The cytokines that develop Th-17 Lymphocytes

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During their development determination of the various T helper cells depends on specific transcription factors for hemopoietic cells. There are exciting new facts about the Th17 cells, albeit there was initial confusion because of differences between the murine and human forms. Perusal of markers for Th17 cells will surely shed light on detailed aspects of renal pathology. To date RORγδ (RORC2) has to be used. In view of their potential aggression, it is not surprising that various controlling influen­ces over Th17 cells (like the interferons alpha and beta) have been identified, and all need to be examined in greater detail. We know that calcitriol (vitamin D receptor agonists) can in­hibit Th-1 helper cells. Now it turns out that calcitriol will also suppress Th17 effector responses. [18] To the nephrologist this sounds like a potential advance in therapeutics.

 
   References Top

1.Murphy KM, Reiner SL. The lineage decision of helper T cells Nat Rev Immunol 2002;2: 933-94.  Back to cited text no. 1      
2.Holdsworth SR, Kitching AR, Tipping PG. Th1 and Th2 T helper subsets affect patterns of in­jury and outcomes in glomerulonephritis. Kidney Int 1999;55:1198-216.  Back to cited text no. 2      
3.Tipping PG, Kitching AR. Glomerulonephritis, Th1 and Th2: what's new? Clin Exp Immunol 2005;142:207-15.  Back to cited text no. 3      
4.van den Berg JG, Weening JJ. Role of the immune system in pathogenesis of idiopathic nephrotic syndrome. Clin Sci 2004;107:125­-36.  Back to cited text no. 4      
5.Laurence A, O'Shea JJ. Th-17 differentiation: of mice and men. Nat Immunol 2007;8:903-5.  Back to cited text no. 5      
6.Mangen PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor beta induces development of the T(H)17 lineage. Nature 2006;441:231-4.  Back to cited text no. 6      
7.Bettelli E, Korn T, Kuchroo VK. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 2007;19:652-7.  Back to cited text no. 7      
8.Crispin JC, Oukka M, Bayliss G, et al. Ex­panded double negative T cells in patients with SLE produce Il-17 and infiltrate the kidneys. J Immunol 2008;181:8761-6.  Back to cited text no. 8      
9.Dong X, Bachman LA, Miller MN, et al. Dendritic cells facilitate accumulation of Il-17 T cells in the kidney following renal obs­truction Kidney Int 2008;74:1294-309.  Back to cited text no. 9      
10.Yuan X, Paez-Cortez J, Schmitt-Knosalla I, et al. A novel role of CD4 Th17 cells in media­ting cardiac allograft rejection and vasculo­pathy. J Exp Med 2008;205:3133-44.  Back to cited text no. 10      
11.Chen Y, Wood KJ. Interleukin 23 and Th17 cells in transplantation. Transplantation 2007; 84:1071-4.  Back to cited text no. 11      
12.Hamour S, Cook T, Iwakura Y, Pusey C, Salama A. Critical role of Il-17 in accelerated nephrotoxic nephritis. Abstr P198 Renal Assocn. Liverpool 2009.  Back to cited text no. 12      
13.Nogueira E, Hamour S, Sawant D, et al. Specific Il-17 are elevated in patients with ANCA associated vasculitis. Nephrol Dial Transpl 2010; 25:2209-17.  Back to cited text no. 13      
14.Fouser L, Wright JF, Dunussi-Joannopoulos K, Collins M. Th17 cytokines and their emerging roles in inflammation and autoimmunity Immunol Revs 2008;226:87-102.  Back to cited text no. 14      
15.Yang XO, Pappu BP, Nurleva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ.. Immunity 2008;28:29-39.  Back to cited text no. 15      
16.Zhou L. TGF(3 induced FoxP3 inhibit T(H)17 cell differentiation by antagonizing RORγδ function. Nature 2008;453:236-40.  Back to cited text no. 16      
17.Wei L, Laurence A, Elias KM, O'Shea JJ. Il­21 is produced by Th17 cells and drives Il-17 production in a Stat3 manner. J Biol Chem 2007;282:34605-10.  Back to cited text no. 17      
18.Tang J, Zhou R, Luger D, et al. Calcitriol suppresses anti-retinal autoimmunity through inhibitory effects on Th17 effector response. J Immunol 2009;182:4624-32.  Back to cited text no. 18      

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E Nigel Wardle
London NW1 8JS
United Kingdom
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