sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease
By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Go...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2177 |
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| author | Shulamit B. Wallach-Dayan Dmytro Petukhov Ronit Ahdut-HaCohen Mark Richter-Dayan Raphael Breuer |
| author_facet | Shulamit B. Wallach-Dayan Dmytro Petukhov Ronit Ahdut-HaCohen Mark Richter-Dayan Raphael Breuer |
| author_sort | Shulamit B. Wallach-Dayan |
| collection | DOAJ |
| description | By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL<sup>+</sup> T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment. |
| first_indexed | 2024-03-09T00:38:36Z |
| format | Article |
| id | doaj.art-8bea225631c44c848205ece03b7fc2d4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:38:36Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8bea225631c44c848205ece03b7fc2d42023-12-11T17:58:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224217710.3390/ijms22042177sFasL—The Key to a Riddle: Immune Responses in Aging Lung and DiseaseShulamit B. Wallach-Dayan0Dmytro Petukhov1Ronit Ahdut-HaCohen2Mark Richter-Dayan3Raphael Breuer4Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelLung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Medical Neurobiology, Institute of Medical Research, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelDepartment of Emergency Medicine, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelLung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelBy dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL<sup>+</sup> T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.https://www.mdpi.com/1422-0067/22/4/2177soluble Fas ligandagingautoimmune responsepulmonary disease |
| spellingShingle | Shulamit B. Wallach-Dayan Dmytro Petukhov Ronit Ahdut-HaCohen Mark Richter-Dayan Raphael Breuer sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease International Journal of Molecular Sciences soluble Fas ligand aging autoimmune response pulmonary disease |
| title | sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease |
| title_full | sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease |
| title_fullStr | sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease |
| title_full_unstemmed | sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease |
| title_short | sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease |
| title_sort | sfasl the key to a riddle immune responses in aging lung and disease |
| topic | soluble Fas ligand aging autoimmune response pulmonary disease |
| url | https://www.mdpi.com/1422-0067/22/4/2177 |
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