Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes
Authors: Huichao Yan
Zan Tong
Chen Dong
Weihuang Liu
Journal: Immunology (2015)
Discipline: IMMUNOLOGY
Keywords: diabetes; interleukin-17A; myeloid-derived suppressor cells; streptozotocin.
Affiliations: School of Basic Medical Sciences, Wuhan University, Wuha, China., Zhongshan Hospital of Hubei Province, Wuha, China., School of Medicines, Tsinghua University, Beijing, China.

Abstract:  Interleukin-17 (IL-17) is a cytokine with critical functions in multiple autoimmune diseases. However, its roles in type I diabetes and the underlying mechanisms remain to be fully elucidated. In the current study, we investigated the impact of IL-17 deficiency on streptozotocin (STZ) -induced diabetes. Il-17(-/-) mice exhibited attenuated hyperglycaemia and insulitis after STZ treatment compared with control mice. The Il-17(-/-) mice had fewer CD8(+) cells infiltrating the pancreas than wild-type controls after STZ injection. Wild-type mice showed increased percentage and number of splenic CD8(+) cells and decreased Gr1(+) CD11b(+) myeloid-derived suppressor cells (MDSC) after STZ treatment, but Il-17(-/-) mice maintained the percentages and numbers of splenic CD8(+) cells and MDSC, suggesting that IL-17 is implicated in STZ-induced cellular immune responses in the spleen. We further purified the MDSC from spleens of STZ-treated mice. Il-17(-/-) MDSC showed increased ability to suppress CD8(+) cell proliferation in vitro compared with wild-type MDSC. Transfer of MDSC to diabetic mice showed that MDSC from Il-17(-/-) mice could ameliorate hyperglycaemia. Moreover, recipients with MDSC from Il-17(-/-) mice had a decreased percentage of CD8(+) cell in the spleen compared with recipients with MDSC from wild-type mice. These data suggest that IL-17 is required in splenic MDSC function after STZ delivery. In summary, our study has revealed a pathogenic role of IL-17 in an STZ-induced diabetes model with important implications for our understanding of IL-17 function in autoimmune diseases. 

Retracted: No

PubPeer comments:
 Figure 2e showed an unexpected similarity between WT and KO, could the authors show the raw data and explain? ![file] , 
 The raw analysis files are attached, as requested. There were significant differences between WT and KO mice in STZ-treated experimental groupsuff08as shown in the figure 2e: KO-STZ and WT-STZuff09uff0cwhile no difference between them in buffer-treated control groupsuff08as shown in the figure 2e: KO-Buffer and WT-Bufferuff09, which were already stated in the paper. The two graphs showed here are from figure 2e: KO-Buffer and WT-Buffer. The CD4 or and CD8 positive cells in the pancreas were relative low under buffer control condition (without STZ drug treatment). There was no significant difference between KO-Buffer and WT-Buffer groups. Overall, these two graphs are different as evidenced by the circled areas. ![file] ![file] ![file] , 
 #2 Undoubtedly there are differences between the two plots, but this does not really address Linaria Rubioides concerns about the observed **similarities**. Here are the plots again, first with reduced saturation (because the color is a distraction), and then with black white reversed so that individual points become more evident, especially in the two upper quadrants. At the bottom, I have superimposed the B W-reversed KO-buffer plot upon the WT-buffer plot, with a slight horizontal offset so that coinciding points are visible with a 3D shadowed appearance. ![file] Coinciding points are cells with identical measurements, present in both data files. Surely there are more of them than one would expect. ,