Saudi Journal of Kidney Diseases and Transplantation

LETTER TO THE EDITOR
Year
: 2010  |  Volume : 21  |  Issue : 5  |  Page : 954--956

Th-17 Lymphocytes


E Nigel Wardle 
 London NW1 8JS, United Kingdom

Correspondence Address:
E Nigel Wardle
London NW1 8JS
United Kingdom




How to cite this article:
Wardle E N. Th-17 Lymphocytes.Saudi J Kidney Dis Transpl 2010;21:954-956


How to cite this URL:
Wardle E N. Th-17 Lymphocytes. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Sep 19 ];21:954-956
Available from: http://www.sjkdt.org/text.asp?2010/21/5/954/68902


Full Text

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 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}

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

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