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Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis

BACKGROUND: Th9 cells are a newly discovered CD4(+) T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are p...

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Autores principales: Yin, Jun-Jie, Hu, Xue-Qiang, Mao, Zhi-Feng, Bao, Jian, Qiu, Wei, Lu, Zheng-Qi, Wu, Hao-Tian, Zhong, Xiao-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407044/
https://www.ncbi.nlm.nih.gov/pubmed/28397727
http://dx.doi.org/10.4103/0366-6999.204110
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author Yin, Jun-Jie
Hu, Xue-Qiang
Mao, Zhi-Feng
Bao, Jian
Qiu, Wei
Lu, Zheng-Qi
Wu, Hao-Tian
Zhong, Xiao-Nan
author_facet Yin, Jun-Jie
Hu, Xue-Qiang
Mao, Zhi-Feng
Bao, Jian
Qiu, Wei
Lu, Zheng-Qi
Wu, Hao-Tian
Zhong, Xiao-Nan
author_sort Yin, Jun-Jie
collection PubMed
description BACKGROUND: Th9 cells are a newly discovered CD4(+) T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic “cross-talk” between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment. METHODS: Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture. RESULTS: Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = −2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = −8.005, P < 0.001; day 15: t = −11.857, P < 0.001; day 20: t = −5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = −5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = −4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = −0.894, P = 0.397; 10 μg/ml: t = −3.348, P = 0.019; 20 μg/ml: t = −7.639, P < 0.001). CONCLUSIONS: This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.
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spelling pubmed-54070442017-05-05 Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis Yin, Jun-Jie Hu, Xue-Qiang Mao, Zhi-Feng Bao, Jian Qiu, Wei Lu, Zheng-Qi Wu, Hao-Tian Zhong, Xiao-Nan Chin Med J (Engl) Original Article BACKGROUND: Th9 cells are a newly discovered CD4(+) T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic “cross-talk” between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment. METHODS: Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture. RESULTS: Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = −2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = −8.005, P < 0.001; day 15: t = −11.857, P < 0.001; day 20: t = −5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = −5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = −4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = −0.894, P = 0.397; 10 μg/ml: t = −3.348, P = 0.019; 20 μg/ml: t = −7.639, P < 0.001). CONCLUSIONS: This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells. Medknow Publications & Media Pvt Ltd 2017-04-20 /pmc/articles/PMC5407044/ /pubmed/28397727 http://dx.doi.org/10.4103/0366-6999.204110 Text en Copyright: © 2017 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Yin, Jun-Jie
Hu, Xue-Qiang
Mao, Zhi-Feng
Bao, Jian
Qiu, Wei
Lu, Zheng-Qi
Wu, Hao-Tian
Zhong, Xiao-Nan
Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title_full Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title_fullStr Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title_full_unstemmed Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title_short Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis
title_sort neutralization of interleukin-9 decreasing mast cells infiltration in experimental autoimmune encephalomyelitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407044/
https://www.ncbi.nlm.nih.gov/pubmed/28397727
http://dx.doi.org/10.4103/0366-6999.204110
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