Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis
The unknown etiology of sarcoidosis, along with the variability in organ involvement and disease course, complicates the effective treatment of this disease. Based on recent studies, the cellular inflammatory pathways involved in granuloma formation are of interest regarding possible new treatment o...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12792 |
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| author | Raisa Kraaijvanger Carmen A. Ambarus Jan Damen Joanne J. van der Vis Karin M. Kazemier Jan C. Grutters Coline H. M. van Moorsel Marcel Veltkamp |
| author_facet | Raisa Kraaijvanger Carmen A. Ambarus Jan Damen Joanne J. van der Vis Karin M. Kazemier Jan C. Grutters Coline H. M. van Moorsel Marcel Veltkamp |
| author_sort | Raisa Kraaijvanger |
| collection | DOAJ |
| description | The unknown etiology of sarcoidosis, along with the variability in organ involvement and disease course, complicates the effective treatment of this disease. Based on recent studies, the cellular inflammatory pathways involved in granuloma formation are of interest regarding possible new treatment options, such as the mechanistic (formerly mammalian) target of rapamycin complex 1 (mTORC1) pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome pathway. The aim of this study was to explore the potential coexpression of these three inflammatory pathways in patients with sarcoidosis and see whether possible differences were related to disease outcome. The tissue of 60 patients with sarcoidosis was used to determine the activity of these three signaling pathways using immunohistochemistry. The activation of NLRP3 was present in 85% of all patients, and the activation of mTORC1 and JAK/STAT was present in 49% and 50% of patients, respectively. Furthermore, the presence of NLRP3 activation at diagnosis was associated with a chronic disease course of sarcoidosis. Our finding of different new conceptual inflammatory tissue phenotypes in sarcoidosis could possibly guide future treatment studies using the available inhibitors of either NLRP3, JAK-STAT, and mTORC1 inhibitors in a more personalized medicine approach. |
| first_indexed | 2024-03-10T23:52:40Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:40Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bd34a56da65d413e9b259561d7bbc5cc2023-11-19T01:29:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161279210.3390/ijms241612792Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with SarcoidosisRaisa Kraaijvanger0Carmen A. Ambarus1Jan Damen2Joanne J. van der Vis3Karin M. Kazemier4Jan C. Grutters5Coline H. M. van Moorsel6Marcel Veltkamp7Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsInterstitial Lung Diseases Center of Excellence, Pathologie DNA, Department of Pathology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsPathologie DNA, Department of Pathology, Jeroen Bosch Hospital, 5223 GZ ‘s-Hertogenbosch, The NetherlandsInterstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsCenter of Translational Immunology, University Medical Center Utrecht, 3508 GA Utrecht, The NetherlandsInterstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsInterstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsInterstitial Lung Diseases Center of Excellence, Department of Pulmonology, St. Antonius Hospital, 3435 CM Nieuwegein, The NetherlandsThe unknown etiology of sarcoidosis, along with the variability in organ involvement and disease course, complicates the effective treatment of this disease. Based on recent studies, the cellular inflammatory pathways involved in granuloma formation are of interest regarding possible new treatment options, such as the mechanistic (formerly mammalian) target of rapamycin complex 1 (mTORC1) pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome pathway. The aim of this study was to explore the potential coexpression of these three inflammatory pathways in patients with sarcoidosis and see whether possible differences were related to disease outcome. The tissue of 60 patients with sarcoidosis was used to determine the activity of these three signaling pathways using immunohistochemistry. The activation of NLRP3 was present in 85% of all patients, and the activation of mTORC1 and JAK/STAT was present in 49% and 50% of patients, respectively. Furthermore, the presence of NLRP3 activation at diagnosis was associated with a chronic disease course of sarcoidosis. Our finding of different new conceptual inflammatory tissue phenotypes in sarcoidosis could possibly guide future treatment studies using the available inhibitors of either NLRP3, JAK-STAT, and mTORC1 inhibitors in a more personalized medicine approach.https://www.mdpi.com/1422-0067/24/16/12792signaling pathwayssarcoidosisphenotypinggranuloma |
| spellingShingle | Raisa Kraaijvanger Carmen A. Ambarus Jan Damen Joanne J. van der Vis Karin M. Kazemier Jan C. Grutters Coline H. M. van Moorsel Marcel Veltkamp Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis International Journal of Molecular Sciences signaling pathways sarcoidosis phenotyping granuloma |
| title | Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis |
| title_full | Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis |
| title_fullStr | Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis |
| title_full_unstemmed | Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis |
| title_short | Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis |
| title_sort | simultaneous assessment of mtorc1 jak stat and nlrp3 inflammasome activation pathways in patients with sarcoidosis |
| topic | signaling pathways sarcoidosis phenotyping granuloma |
| url | https://www.mdpi.com/1422-0067/24/16/12792 |
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