Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease
Chronic beryllium disease (CBD) is a debilitating pulmonary disorder that occurs due to persistent exposure to beryllium (Be) particles in the workplace. Be-exposure causes activation of the innate immune system, resulting in the secretion of interleukins and chemokines that drive the accumulation o...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1479348/full |
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| author | Joseph M. Gaballa Caley Valdez Douglas G. Mack Faiz Minhajuddin Masoom Raza Tabrez A. Mohammad Allison K. Martin Andrew Getahun Charles A. Dinarello Andrew P. Fontenot Shaikh M. Atif |
| author_facet | Joseph M. Gaballa Caley Valdez Douglas G. Mack Faiz Minhajuddin Masoom Raza Tabrez A. Mohammad Allison K. Martin Andrew Getahun Charles A. Dinarello Andrew P. Fontenot Shaikh M. Atif |
| author_sort | Joseph M. Gaballa |
| collection | DOAJ |
| description | Chronic beryllium disease (CBD) is a debilitating pulmonary disorder that occurs due to persistent exposure to beryllium (Be) particles in the workplace. Be-exposure causes activation of the innate immune system, resulting in the secretion of interleukins and chemokines that drive the accumulation of B and T cells in the lungs. However, the mechanisms by which innate molecules influence the recruitment of B cells and B cell-mediated protection in CBD are poorly understood. In this study, we employed multiple approaches to examine the role of innate immune signaling and CD4+ T cells in B cell recruitment and function in the lungs. We show that the absence or blocking of IL-1R1 signaling prevents the recruitment of B cells to the lungs of BeO-exposed mice. Additionally, we show that B cell recruitment to the lungs depends on the chemokine receptor, CXCR5, and CD4+ T cells. In BeO-exposed mice, lung B cells down-regulate IgM but showed an increased IgD and CD44 surface expression. Further, RNA sequencing of pulmonary tissue-specific B cells in CBD revealed distinct gene signatures compared to splenic B cells, with increased expression of pathways involved in antigen presentation, tight junction interactions, and interferon signaling. Overall, our study shows that B cell recruitment and aggregate formation during CBD depend on sequential activation of innate and adaptive immune responses. |
| format | Article |
| id | doaj-art-0ac43f8d74484d6f83b67ac2bb288b72 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-0ac43f8d74484d6f83b67ac2bb288b722025-01-28T05:10:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14793481479348Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium diseaseJoseph M. Gaballa0Caley Valdez1Douglas G. Mack2Faiz Minhajuddin3Masoom Raza4Tabrez A. Mohammad5Allison K. Martin6Andrew Getahun7Charles A. Dinarello8Andrew P. Fontenot9Shaikh M. Atif10Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesGreehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesChronic beryllium disease (CBD) is a debilitating pulmonary disorder that occurs due to persistent exposure to beryllium (Be) particles in the workplace. Be-exposure causes activation of the innate immune system, resulting in the secretion of interleukins and chemokines that drive the accumulation of B and T cells in the lungs. However, the mechanisms by which innate molecules influence the recruitment of B cells and B cell-mediated protection in CBD are poorly understood. In this study, we employed multiple approaches to examine the role of innate immune signaling and CD4+ T cells in B cell recruitment and function in the lungs. We show that the absence or blocking of IL-1R1 signaling prevents the recruitment of B cells to the lungs of BeO-exposed mice. Additionally, we show that B cell recruitment to the lungs depends on the chemokine receptor, CXCR5, and CD4+ T cells. In BeO-exposed mice, lung B cells down-regulate IgM but showed an increased IgD and CD44 surface expression. Further, RNA sequencing of pulmonary tissue-specific B cells in CBD revealed distinct gene signatures compared to splenic B cells, with increased expression of pathways involved in antigen presentation, tight junction interactions, and interferon signaling. Overall, our study shows that B cell recruitment and aggregate formation during CBD depend on sequential activation of innate and adaptive immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1479348/fullinterleukinsIL-1IL-1RaAnakinrachemokinesinflammation |
| spellingShingle | Joseph M. Gaballa Caley Valdez Douglas G. Mack Faiz Minhajuddin Masoom Raza Tabrez A. Mohammad Allison K. Martin Andrew Getahun Charles A. Dinarello Andrew P. Fontenot Shaikh M. Atif Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease Frontiers in Immunology interleukins IL-1 IL-1Ra Anakinra chemokines inflammation |
| title | Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease |
| title_full | Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease |
| title_fullStr | Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease |
| title_full_unstemmed | Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease |
| title_short | Interleukin-1 signaling and CD4+ T cells control B cell recruitment to the lungs in chronic beryllium disease |
| title_sort | interleukin 1 signaling and cd4 t cells control b cell recruitment to the lungs in chronic beryllium disease |
| topic | interleukins IL-1 IL-1Ra Anakinra chemokines inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1479348/full |
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