Differentiation and Recruitment of IL-22–Producing Helper T Cells Stimulated by Pleural Mesothelial Cells in Tuberculous Pleurisy
Authors: Xian-Zhi Xiong
Zhi-Jian Ye
Wei-Bing Yang
Rong-Hui Du
Bo Huang
Ming-Li Yuan
Huan-Zhong Shi
Qiong Zhou
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: Th22 cells; tuberculous pleural effusion; differentiation; immune regulation; proinflammatory cytokines
Affiliations: Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract:  Rationale: IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown. Objectives: To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space. Methods: The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed. Measurements and main results: Th22 cells were significantly higher in TPE than in blood. IL-1β, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen. Conclusions: The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation. 

Retracted: No

PubPeer comments:
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 #1 Dear Actinopolyspora Biskrensis, Thank you for your comments. Two sets of experiments for the articles u2018PLoS ONE 2012, 7, e31710u2019 and u2018Am J Respir Crit Care Med 2012u2019 were conducted during the same period. ![![](http: )](http: )![file] Here, we overlapped PLoS One Fig. 7B and AJRCCM Fig. 8B to compare IL-9 and IL-22 data. As indicated in the merged image, IL-9 data in PLoS ONE Fig. 7B were very different from IL-22 data in AJRCCM Fig. 8B. ![![](http: )](http: )![file] Each panel of either Plos One Fig. 7A or AJRCCM Fig. 8A was one representative microscopy picture of five independent experiments of pleural mesothelial cells (PMCs) seeded in 12-well plates. IFN-u03b3 was added in both experiments to serve as control, since its effect on long-term restoration of PMCs had been known. The right middle panel of AJRCCM Fig. 8A was taken from PMCs cultured for 7 days, and the right bottom panel of PLoS One Fig. 7A was taken at day 14 from the same well. One can tell that two panels are not identical, and we label some differences using three circles with different colors for examples; actually, the other substaintial differeces can be seen throughout the images. , 
 #2 ![![](http: )](http: )![file] AJRCCM Fig. 8A, left panels were medium control microscopy pictures. The left middle panel was taken from PMCs cultured under control condition at 7 days, and left bottom panel was taken at day 14 from the same well. One can tell that the corresponding areas in the two images are not identical, and we label some differences using three circles with different colors for examples; actually, the other substantial differences can be seen throughout the corresponding field. , 
 #3 Similar situations were seen in AJRCCM Fig. 6C, each panel was one representative microscopy picture of five independent PMC early-stage repairing experiments. As indicated in bottom panels, addition of antiu2013IFN-u03b3 mAb into TPE significantly improved PMC wound healing, resulting in PMC confluence at 32 hr (bottom, second from right), further 16-hr culture did not exert extra effect (right bottom panel). Bottom, second from right panel was taken at 32 hr, and right bottom panel was taken at 48 hr from the same well. , 
 #4 Sorry, but I don t think the explanation of different colors is an adequate explanation. Clearly these are the same cells. The fact that you can highlight some areas of the pictures that are not identical does not detract from the fact that some areas of the pictures ARE more identical similar than is possible purely by chance. The likelihood that the cells could have come out looking so similar by pure coincidence, is infinitesimally small. Is that what you are claiming? ,