The Role of B Cells in Scleroderma Lung Disease Pathogenesis
Systemic sclerosis (SSc) is a chronic, autoimmune, multisystem disease characterized by tissue fibrosis that, apart from the skin, may affect the lungs among other organs. B cells have been found in tissue lymphocytic infiltrates; in the lungs are encountered in lymphoid aggregates. The abnormal and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.936182/full |
| _version_ | 1818112046465548288 |
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| author | Stamatis-Nick C. Liossis Stamatis-Nick C. Liossis Chrysanthi Staveri |
| author_facet | Stamatis-Nick C. Liossis Stamatis-Nick C. Liossis Chrysanthi Staveri |
| author_sort | Stamatis-Nick C. Liossis |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is a chronic, autoimmune, multisystem disease characterized by tissue fibrosis that, apart from the skin, may affect the lungs among other organs. B cells have been found in tissue lymphocytic infiltrates; in the lungs are encountered in lymphoid aggregates. The abnormal and hyperreactive B cell in SSc may initiate and perpetuate the fibrotic process via incompletely understood mechanisms. Studies in animal models of SSc have demonstrated that B cell dysregulation is an early event in disease pathogenesis. Functional disturbances of BCR signaling such as decreased inhibitory CD22 signal transduction or augmented CD19-mediated signaling result in prolonged B cell activation. Antagonism of BAFF, a cytokine known for his central role in B cell survival and maturation, not only suppresses the production of fibrogenic cytokines such as IL-6 and IL-10, but also amplifies antifibrogenic cytokine secretion such as IFN-γ and it finally contributes to skin fibrosis attenuation. B cells subsets in SSc patients display several abnormalities. Naïve B cells are increased, in contrast to switched memory B cells that are not only decreased but also activated. Disturbances in the expression of molecules that are involved in B cell tuning have also been described. Interestingly, a distinct B cell population characterized by anergy and exhaustion has been found to be increased in patients with SSc-ILD. Another B cell subset, the CD30+GM-Beff, is capable to differentiate monocytes to dendritic cells and is increased in SSc patients with ILD. Of note, patients with SSc-ILD exhibit increased expression of the inhibitory receptor FcγRIIB on naïve and double negative B cells aiming perhaps to counterbalance the abnormal B cell activation. Studies of B cell targeted treatments have demonstrated promising clinical efficacy. Therefore, B cell eliminating therapies could be integrated into the therapeutic armamentarium of patients suffering from SSc-ILD aiming to at least stabilize the fibrotic lung process. |
| first_indexed | 2024-12-11T03:12:43Z |
| format | Article |
| id | doaj.art-3d96b5a0319a49188b93de923d14c768 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-11T03:12:43Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-3d96b5a0319a49188b93de923d14c7682022-12-22T01:22:50ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-07-01910.3389/fmed.2022.936182936182The Role of B Cells in Scleroderma Lung Disease PathogenesisStamatis-Nick C. Liossis0Stamatis-Nick C. Liossis1Chrysanthi Staveri2Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, Patras, GreeceDivision of Rheumatology, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, Patras, GreeceSystemic sclerosis (SSc) is a chronic, autoimmune, multisystem disease characterized by tissue fibrosis that, apart from the skin, may affect the lungs among other organs. B cells have been found in tissue lymphocytic infiltrates; in the lungs are encountered in lymphoid aggregates. The abnormal and hyperreactive B cell in SSc may initiate and perpetuate the fibrotic process via incompletely understood mechanisms. Studies in animal models of SSc have demonstrated that B cell dysregulation is an early event in disease pathogenesis. Functional disturbances of BCR signaling such as decreased inhibitory CD22 signal transduction or augmented CD19-mediated signaling result in prolonged B cell activation. Antagonism of BAFF, a cytokine known for his central role in B cell survival and maturation, not only suppresses the production of fibrogenic cytokines such as IL-6 and IL-10, but also amplifies antifibrogenic cytokine secretion such as IFN-γ and it finally contributes to skin fibrosis attenuation. B cells subsets in SSc patients display several abnormalities. Naïve B cells are increased, in contrast to switched memory B cells that are not only decreased but also activated. Disturbances in the expression of molecules that are involved in B cell tuning have also been described. Interestingly, a distinct B cell population characterized by anergy and exhaustion has been found to be increased in patients with SSc-ILD. Another B cell subset, the CD30+GM-Beff, is capable to differentiate monocytes to dendritic cells and is increased in SSc patients with ILD. Of note, patients with SSc-ILD exhibit increased expression of the inhibitory receptor FcγRIIB on naïve and double negative B cells aiming perhaps to counterbalance the abnormal B cell activation. Studies of B cell targeted treatments have demonstrated promising clinical efficacy. Therefore, B cell eliminating therapies could be integrated into the therapeutic armamentarium of patients suffering from SSc-ILD aiming to at least stabilize the fibrotic lung process.https://www.frontiersin.org/articles/10.3389/fmed.2022.936182/fullB cellscleroderma (systemic sclerosis)interstial lung diseasepathogenesishuman |
| spellingShingle | Stamatis-Nick C. Liossis Stamatis-Nick C. Liossis Chrysanthi Staveri The Role of B Cells in Scleroderma Lung Disease Pathogenesis Frontiers in Medicine B cell scleroderma (systemic sclerosis) interstial lung disease pathogenesis human |
| title | The Role of B Cells in Scleroderma Lung Disease Pathogenesis |
| title_full | The Role of B Cells in Scleroderma Lung Disease Pathogenesis |
| title_fullStr | The Role of B Cells in Scleroderma Lung Disease Pathogenesis |
| title_full_unstemmed | The Role of B Cells in Scleroderma Lung Disease Pathogenesis |
| title_short | The Role of B Cells in Scleroderma Lung Disease Pathogenesis |
| title_sort | role of b cells in scleroderma lung disease pathogenesis |
| topic | B cell scleroderma (systemic sclerosis) interstial lung disease pathogenesis human |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.936182/full |
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