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Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions

IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA pati...

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Autores principales: Heim, Jana, Almanzar, Giovanni, Schmalzing, Marc, Gernert, Michael, Tony, Hans-Peter, Prelog, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117786/
https://www.ncbi.nlm.nih.gov/pubmed/33995403
http://dx.doi.org/10.3389/fimmu.2021.668095
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author Heim, Jana
Almanzar, Giovanni
Schmalzing, Marc
Gernert, Michael
Tony, Hans-Peter
Prelog, Martina
author_facet Heim, Jana
Almanzar, Giovanni
Schmalzing, Marc
Gernert, Michael
Tony, Hans-Peter
Prelog, Martina
author_sort Heim, Jana
collection PubMed
description IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA patients compared to immunologically healthy individuals and whether autocrine mechanisms are able to enhance Th9 polarization. Further, parallel pathways of induction of IL-17-producing cells with Th9 phenotype have to be distinguished from exclusively Th9-inductive mechanisms. Thus, the present study aimed to determine the parameters of Th9 induction by simulation in a standardized inflammatory cytokine milieu.Peripheral naive and non-naive T cells of RA patients and healthy donors (HD) were cultured under Th9 and Th17-driving conditions and phenotypically analyzed by flow cytometry and molecular analysis.Our findings indicate a similar differentiation pathway of Th9 and Th17 cells and similar distributions of IL-9+ T cells in RA and HD regardless of Th9- or Th17-promoting cytokine milieus. Whereas the magnitude and direction of Th9- or Th17-polarization was about the same in RA and HD, IL-17+ CD4+ T cells were significantly stimulated by Th17-inducing conditions in HD. In conclusion, the results indicate that Th9- and Th17-inducing cytokine conditions mimicking autoimmune inflammation in RA may have similar stimulatory effects regarding polarization of peripheral naive and non-naive T cells into Th9 or Th17 cells. The results suggest that the differentiation of Th9 cells may be also induced by Th17-driving conditions.
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spelling pubmed-81177862021-05-14 Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions Heim, Jana Almanzar, Giovanni Schmalzing, Marc Gernert, Michael Tony, Hans-Peter Prelog, Martina Front Immunol Immunology IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA patients compared to immunologically healthy individuals and whether autocrine mechanisms are able to enhance Th9 polarization. Further, parallel pathways of induction of IL-17-producing cells with Th9 phenotype have to be distinguished from exclusively Th9-inductive mechanisms. Thus, the present study aimed to determine the parameters of Th9 induction by simulation in a standardized inflammatory cytokine milieu.Peripheral naive and non-naive T cells of RA patients and healthy donors (HD) were cultured under Th9 and Th17-driving conditions and phenotypically analyzed by flow cytometry and molecular analysis.Our findings indicate a similar differentiation pathway of Th9 and Th17 cells and similar distributions of IL-9+ T cells in RA and HD regardless of Th9- or Th17-promoting cytokine milieus. Whereas the magnitude and direction of Th9- or Th17-polarization was about the same in RA and HD, IL-17+ CD4+ T cells were significantly stimulated by Th17-inducing conditions in HD. In conclusion, the results indicate that Th9- and Th17-inducing cytokine conditions mimicking autoimmune inflammation in RA may have similar stimulatory effects regarding polarization of peripheral naive and non-naive T cells into Th9 or Th17 cells. The results suggest that the differentiation of Th9 cells may be also induced by Th17-driving conditions. Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC8117786/ /pubmed/33995403 http://dx.doi.org/10.3389/fimmu.2021.668095 Text en Copyright © 2021 Heim, Almanzar, Schmalzing, Gernert, Tony and Prelog https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Heim, Jana
Almanzar, Giovanni
Schmalzing, Marc
Gernert, Michael
Tony, Hans-Peter
Prelog, Martina
Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title_full Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title_fullStr Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title_full_unstemmed Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title_short Induction of IL-9 in Peripheral Lymphocytes of Rheumatoid Arthritis Patients and Healthy Donors by Th17-Inducing Cytokine Conditions
title_sort induction of il-9 in peripheral lymphocytes of rheumatoid arthritis patients and healthy donors by th17-inducing cytokine conditions
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117786/
https://www.ncbi.nlm.nih.gov/pubmed/33995403
http://dx.doi.org/10.3389/fimmu.2021.668095
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