Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease of unknown etiology. Myofibroblasts are organized in peculiar subepithelial fibroblasts foci (FF), where they abnormally persist and exclude lymphocytes by unclear mechanisms. FF are the source of an excessive extrace...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.820347/full |
| _version_ | 1818897110034022400 |
|---|---|
| author | Leslie Chavez-Galan Carina Becerril Andy Ruiz Lucero A. Ramon-Luing José Cisneros Martha Montaño Alfonso Salgado Carlos Ramos Ivette Buendía-Roldán Annie Pardo Moisés Selman |
| author_facet | Leslie Chavez-Galan Carina Becerril Andy Ruiz Lucero A. Ramon-Luing José Cisneros Martha Montaño Alfonso Salgado Carlos Ramos Ivette Buendía-Roldán Annie Pardo Moisés Selman |
| author_sort | Leslie Chavez-Galan |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease of unknown etiology. Myofibroblasts are organized in peculiar subepithelial fibroblasts foci (FF), where they abnormally persist and exclude lymphocytes by unclear mechanisms. FF are the source of an excessive extracellular matrix, which results in progressive stiffening and destruction of the lung architecture. We hypothesized that the absence of T cells inside the FF could be related, at least partially, to an inefficient function of lymphocytes induced by IPF fibroblasts. Here, we evaluated the effect of a supernatant from IPF fibroblasts on T-cell apoptosis and migration capacity. Data showed that IPF fibroblasts secrete pro-apoptotic molecules (both from extrinsic and intrinsic pathways), generating a microenvironment that induces apoptosis of T cells at 3 h of culture, despite a weak anti-apoptotic profile exhibited by these T cells. At 24 h of culture, the supernatants from both IPF and control fibroblasts provoked T-cell death. However, at this time of culture, IPF fibroblasts caused a marked decrease in T-cell migration; in contrast, control lung fibroblasts induced an increase of T-cell migration. The reduction of T-cell migratory capacity provoked by IPF fibroblasts was associated with a negative regulation of RHOA and ROCK, two essential GTPases for migration, and was independent of the expression of chemokine receptors. In conclusion, our findings demonstrate that IPF fibroblasts/myofibroblasts induce apoptosis and affect T-cell migration, revealing a mechanism involved in the virtual absence of T lymphocytes inside the FF. |
| first_indexed | 2024-12-19T19:10:58Z |
| format | Article |
| id | doaj.art-0c05597472494e479090bf82e392d5eb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T19:10:58Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0c05597472494e479090bf82e392d5eb2022-12-21T20:09:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.820347820347Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T LymphocytesLeslie Chavez-Galan0Carina Becerril1Andy Ruiz2Lucero A. Ramon-Luing3José Cisneros4Martha Montaño5Alfonso Salgado6Carlos Ramos7Ivette Buendía-Roldán8Annie Pardo9Moisés Selman10Instituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoFacultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, MexicoInstituto Nacional de Enfermedades Respiratorias, “Ismael Cosío Villegas”, Mexico City, MexicoIdiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease of unknown etiology. Myofibroblasts are organized in peculiar subepithelial fibroblasts foci (FF), where they abnormally persist and exclude lymphocytes by unclear mechanisms. FF are the source of an excessive extracellular matrix, which results in progressive stiffening and destruction of the lung architecture. We hypothesized that the absence of T cells inside the FF could be related, at least partially, to an inefficient function of lymphocytes induced by IPF fibroblasts. Here, we evaluated the effect of a supernatant from IPF fibroblasts on T-cell apoptosis and migration capacity. Data showed that IPF fibroblasts secrete pro-apoptotic molecules (both from extrinsic and intrinsic pathways), generating a microenvironment that induces apoptosis of T cells at 3 h of culture, despite a weak anti-apoptotic profile exhibited by these T cells. At 24 h of culture, the supernatants from both IPF and control fibroblasts provoked T-cell death. However, at this time of culture, IPF fibroblasts caused a marked decrease in T-cell migration; in contrast, control lung fibroblasts induced an increase of T-cell migration. The reduction of T-cell migratory capacity provoked by IPF fibroblasts was associated with a negative regulation of RHOA and ROCK, two essential GTPases for migration, and was independent of the expression of chemokine receptors. In conclusion, our findings demonstrate that IPF fibroblasts/myofibroblasts induce apoptosis and affect T-cell migration, revealing a mechanism involved in the virtual absence of T lymphocytes inside the FF.https://www.frontiersin.org/articles/10.3389/fimmu.2022.820347/fullidiopathic pulmonary fibrosisT cellsapoptosismigrationfibrotic focus |
| spellingShingle | Leslie Chavez-Galan Carina Becerril Andy Ruiz Lucero A. Ramon-Luing José Cisneros Martha Montaño Alfonso Salgado Carlos Ramos Ivette Buendía-Roldán Annie Pardo Moisés Selman Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes Frontiers in Immunology idiopathic pulmonary fibrosis T cells apoptosis migration fibrotic focus |
| title | Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes |
| title_full | Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes |
| title_fullStr | Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes |
| title_full_unstemmed | Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes |
| title_short | Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes |
| title_sort | fibroblasts from idiopathic pulmonary fibrosis induce apoptosis and reduce the migration capacity of t lymphocytes |
| topic | idiopathic pulmonary fibrosis T cells apoptosis migration fibrotic focus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.820347/full |
| work_keys_str_mv | AT lesliechavezgalan fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT carinabecerril fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT andyruiz fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT luceroaramonluing fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT josecisneros fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT marthamontano fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT alfonsosalgado fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT carlosramos fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT ivettebuendiaroldan fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT anniepardo fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes AT moisesselman fibroblastsfromidiopathicpulmonaryfibrosisinduceapoptosisandreducethemigrationcapacityoftlymphocytes |