Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes

Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat. Previous studies have found a positive correlation between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a sy...

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Autores principales: Cao, Qiuhua, Gao, Xinghua, Lin, Yanting, Yue, Chongxiu, Wang, Yue, Quan, Fei, Zhang, Zixuan, Liu, Xiaoxuan, Lu, Yuan, Zhan, Yanling, Yang, Hongbao, Li, Xianjing, Qin, Di, Birnbaumer, Lutz, Hao, Kun, Yang, Yong
Formato: Artículo
Lenguaje:Inglés
Publicado: Ivyspring International Publisher 2020
Materias:
COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9854
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-9854
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
spellingShingle COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
Cao, Qiuhua
Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
topic_facet COLITIS
TIMOPENTINA
TRATAMIENTO MEDICO
LINFOCITOS
description Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat. Previous studies have found a positive correlation between thymic atrophy and colitis severity. It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active domain of the thymopoietin, on colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis mice were treated with TP5 by subcutaneous injection. Body weight, colon length, colon weight, immune organ index, disease activity index (DAI) score, and the peripheral blood profile were examined. The immune cells of the spleen and colon were analyzed by flow cytometry. Histology was performed on isolated colon tissues for cytokine analysis. Bacterial DNA was extracted from mouse colonic feces to assess the intestinal microbiota. Intestinal lamina propria mononuclear cells (LPMCs), HCT116, CT26, and splenocytes were cultured and treated with TP5. Results: TP5 treatment increased the body weight and colon length, decreased the DAI score, and restored colon architecture of colitic mice. TP5 also decreased the infiltration of immune cells and expression levels of pro-inflammatory cytokines such as IL-6. Importantly, the damaged thymus and compromised lymphocytes in peripheral blood were significantly restored by TP5. Also, the production of IL-22, both in innate and adaptive lymphoid cells, was triggered by TP5. Given the critical role of IL-22 in mucosal host defense, we tested the effect of TP5 on mucus barrier and gut microbiota and found that the number of goblet cells and the level of Mucin-2 expression were restored, and the composition of the gut microbiome was normalized after TP5 treatment. The critical role of IL-22 in the protective effect of TP5 on colitis was further confirmed by administering the anti-IL-22 antibody (αIL-22), which completely abolished the effect of TP5. Furthermore, TP5 significantly increased the expression level of retinoic acid receptor-related orphan receptor γ (RORγt), a transcription factor for IL-22. Consistent with this, RORγt inhibitor abrogated the upregulation of IL-22 induced by TP5. Conclusion: TP5 exerts a protective effect on DSS-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes. This study delineates TP5 as an immunomodulator that may be a potential drug for the treatment of UC.
format Artículo
author Cao, Qiuhua
Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
author_facet Cao, Qiuhua
Gao, Xinghua
Lin, Yanting
Yue, Chongxiu
Wang, Yue
Quan, Fei
Zhang, Zixuan
Liu, Xiaoxuan
Lu, Yuan
Zhan, Yanling
Yang, Hongbao
Li, Xianjing
Qin, Di
Birnbaumer, Lutz
Hao, Kun
Yang, Yong
author_sort Cao, Qiuhua
title Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_short Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_full Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_fullStr Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_full_unstemmed Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
title_sort thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of il-22 in both innate and adaptive lymphocytes
publisher Ivyspring International Publisher
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9854
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