The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses
IntroductionAnandamide (AEA) is an endocannabinoid that has recently been recognized as a regulator of various inflammatory diseases as well as cancer. While AEA was thought to predominantly engage cannabinoid (CB) receptors, recent findings suggest that, given its protective anti-inflammatory role...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1528759/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846114912489701376 |
|---|---|
| author | Anastasiia Kiprina Tom Teichmann Tom Teichmann Virna Margarita Martín Giménez Wenqing Xu Fiona Sailer Maike Windbergs Walter Manucha Walter Manucha Andreas Weigert Ralf P. Brandes Ralf P. Brandes |
| author_facet | Anastasiia Kiprina Tom Teichmann Tom Teichmann Virna Margarita Martín Giménez Wenqing Xu Fiona Sailer Maike Windbergs Walter Manucha Walter Manucha Andreas Weigert Ralf P. Brandes Ralf P. Brandes |
| author_sort | Anastasiia Kiprina |
| collection | DOAJ |
| description | IntroductionAnandamide (AEA) is an endocannabinoid that has recently been recognized as a regulator of various inflammatory diseases as well as cancer. While AEA was thought to predominantly engage cannabinoid (CB) receptors, recent findings suggest that, given its protective anti-inflammatory role in pathological conditions, anandamide may engage not only CB receptors.MethodsIn this study, we studied the role of exogenous AEA in a mouse AirPouch model of acute inflammation by examining immune cell infiltrates by flow cytometry. Human primary immune cells were used to validate findings towards immune cell activation and migration by flow cytometry and bead-based ELISA.ResultsWe found that AEA decreases the acute infiltration of myeloid cells including granulocytes and monocytes into the inflamed area, but unexpectedly increases the number of T cells at the site of inflammation. This was related to AEA signaling through nuclear receptor subfamily 4A (NR4A) transcription factors rather than CB receptors. Exploring regulatory mechanisms in the human system, we found that AEA broadly inhibits the migratory capacity of immune cells, arguing for blocked emigration of T cells from the inflamed tissue. Taking a closer look at the impact of AEA on T cells revealed that AEA profoundly alters the activation and exhaustion status of CD4+ T and CD8+ T cells, thereby strongly inhibiting TH17 responses, while not altering TH1 differentiation.DiscussionThese data suggest that AEA has the potential to block chronic inflammation without influencing crucial anti-viral and anti-microbial immune defense mechanisms, and may therefore be an attractive molecule to interfere with the establishment of chronic inflammation. |
| format | Article |
| id | doaj-art-d4df340f1faf4d76a1db32af2fb1c68b |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-d4df340f1faf4d76a1db32af2fb1c68b2024-12-20T06:29:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.15287591528759The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responsesAnastasiia Kiprina0Tom Teichmann1Tom Teichmann2Virna Margarita Martín Giménez3Wenqing Xu4Fiona Sailer5Maike Windbergs6Walter Manucha7Walter Manucha8Andreas Weigert9Ralf P. Brandes10Ralf P. Brandes11Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, GermanyInstitute for Cardiovascular Physiology, Goethe University Frankfurt, Frankfurt, GermanyGerman Centre of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, GermanyInstituto de Investigaciones en Ciencias Químicas, Facultad de Ciencias Químicas y Tecnológicas, Universidad Católica de Cuyo, San Juan, ArgentinaInstitute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt, GermanyInstituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Mendoza, ArgentinaDepartamento de Patología, Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, ArgentinaInstitute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, GermanyInstitute for Cardiovascular Physiology, Goethe University Frankfurt, Frankfurt, GermanyGerman Centre of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, GermanyIntroductionAnandamide (AEA) is an endocannabinoid that has recently been recognized as a regulator of various inflammatory diseases as well as cancer. While AEA was thought to predominantly engage cannabinoid (CB) receptors, recent findings suggest that, given its protective anti-inflammatory role in pathological conditions, anandamide may engage not only CB receptors.MethodsIn this study, we studied the role of exogenous AEA in a mouse AirPouch model of acute inflammation by examining immune cell infiltrates by flow cytometry. Human primary immune cells were used to validate findings towards immune cell activation and migration by flow cytometry and bead-based ELISA.ResultsWe found that AEA decreases the acute infiltration of myeloid cells including granulocytes and monocytes into the inflamed area, but unexpectedly increases the number of T cells at the site of inflammation. This was related to AEA signaling through nuclear receptor subfamily 4A (NR4A) transcription factors rather than CB receptors. Exploring regulatory mechanisms in the human system, we found that AEA broadly inhibits the migratory capacity of immune cells, arguing for blocked emigration of T cells from the inflamed tissue. Taking a closer look at the impact of AEA on T cells revealed that AEA profoundly alters the activation and exhaustion status of CD4+ T and CD8+ T cells, thereby strongly inhibiting TH17 responses, while not altering TH1 differentiation.DiscussionThese data suggest that AEA has the potential to block chronic inflammation without influencing crucial anti-viral and anti-microbial immune defense mechanisms, and may therefore be an attractive molecule to interfere with the establishment of chronic inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2024.1528759/fullAEAendocannabinoidsT cellsinflammationlipids |
| spellingShingle | Anastasiia Kiprina Tom Teichmann Tom Teichmann Virna Margarita Martín Giménez Wenqing Xu Fiona Sailer Maike Windbergs Walter Manucha Walter Manucha Andreas Weigert Ralf P. Brandes Ralf P. Brandes The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses Frontiers in Pharmacology AEA endocannabinoids T cells inflammation lipids |
| title | The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses |
| title_full | The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses |
| title_fullStr | The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses |
| title_full_unstemmed | The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses |
| title_short | The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses |
| title_sort | endocannabinoid anandamide prevents th17 programming of activated t lymphocytes while preserving th1 responses |
| topic | AEA endocannabinoids T cells inflammation lipids |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1528759/full |
| work_keys_str_mv | AT anastasiiakiprina theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT tomteichmann theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT tomteichmann theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT virnamargaritamartingimenez theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT wenqingxu theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT fionasailer theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT maikewindbergs theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT waltermanucha theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT waltermanucha theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT andreasweigert theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT ralfpbrandes theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT ralfpbrandes theendocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT anastasiiakiprina endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT tomteichmann endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT tomteichmann endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT virnamargaritamartingimenez endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT wenqingxu endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT fionasailer endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT maikewindbergs endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT waltermanucha endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT waltermanucha endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT andreasweigert endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT ralfpbrandes endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses AT ralfpbrandes endocannabinoidanandamidepreventsth17programmingofactivatedtlymphocyteswhilepreservingth1responses |