Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation. Hadebe, S., Savulescu, A. F., Khumalo, J., Jones, K., Mangali, S., Mthembu, N., Musaigwa, F., Maepa, W., Ndlovu, H., Ngomti, A., Scibiorek, M., Okendo, J., & Brombacher, F. bioRxiv, jan, 2023. ![Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Allergic asthma is a disease driven by T helper 2 (Th2) cells, eosinophilia, airway hyperresponsiveness (AHR) and IgE-secreting B cells. Asthma is largely controlled by corticosteroids and beta 2 adregenic receptor agonists that target and relax airway smooth muscle (ASM). Immunoglobulin M (IgM) isotype secreted by naive B cells is important for class switching but may have other undefined functions. We investigated the role of IgM in a house dust mite (HDM)-induced Th2 allergic asthma model. We sensitised wild-type (WT) and IgM-deficient (IgM-/-) mice with HDM and measured AHR, and Th2 responses. We performed RNA sequencing on the whole lung of WT and IgM-/- mice sensitised to saline or HDM. We validated our AHR data on human ASM by deleting genes using CRISPR and measuring contraction by single-cell force cytometry. We found IgM to be essential in AHR but not Th2 airway inflammation or eosinophilia. RNA sequencing of lung tissue suggested that IgM regulated AHR through modulating brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1) and other genes. Deletion of BAIAP2L1 led to a differential reduction in human ASM contraction when stimulated with TNF-alpha and acetylcholine, but not IL-13. These findings have implications for future treatment of asthma beyond current therapies.Competing Interest StatementThe authors have declared no competing interest.
@article{Hadebe2023,
abstract = {Allergic asthma is a disease driven by T helper 2 (Th2) cells, eosinophilia, airway hyperresponsiveness (AHR) and IgE-secreting B cells. Asthma is largely controlled by corticosteroids and beta 2 adregenic receptor agonists that target and relax airway smooth muscle (ASM). Immunoglobulin M (IgM) isotype secreted by naive B cells is important for class switching but may have other undefined functions. We investigated the role of IgM in a house dust mite (HDM)-induced Th2 allergic asthma model. We sensitised wild-type (WT) and IgM-deficient (IgM-/-) mice with HDM and measured AHR, and Th2 responses. We performed RNA sequencing on the whole lung of WT and IgM-/- mice sensitised to saline or HDM. We validated our AHR data on human ASM by deleting genes using CRISPR and measuring contraction by single-cell force cytometry. We found IgM to be essential in AHR but not Th2 airway inflammation or eosinophilia. RNA sequencing of lung tissue suggested that IgM regulated AHR through modulating brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1) and other genes. Deletion of BAIAP2L1 led to a differential reduction in human ASM contraction when stimulated with TNF-alpha and acetylcholine, but not IL-13. These findings have implications for future treatment of asthma beyond current therapies.Competing Interest StatementThe authors have declared no competing interest.},
author = {Hadebe, Sabelo and Savulescu, Anca Flavia and Khumalo, Jermaine and Jones, Katelyn and Mangali, Sandisiwe and Mthembu, Nontobeko and Musaigwa, Fungai and Maepa, Welcome and Ndlovu, Hlumani and Ngomti, Amkele and Scibiorek, Martyna and Okendo, Javan and Brombacher, Frank},
doi = {10.1101/2023.08.02.551636},
journal = {bioRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jan},
pages = {2023.08.02.551636},
title = {{Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation.}},
url = {http://biorxiv.org/content/early/2023/08/05/2023.08.02.551636.abstract},
year = {2023}
}
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We sensitised wild-type (WT) and IgM-deficient (IgM-/-) mice with HDM and measured AHR, and Th2 responses. We performed RNA sequencing on the whole lung of WT and IgM-/- mice sensitised to saline or HDM. We validated our AHR data on human ASM by deleting genes using CRISPR and measuring contraction by single-cell force cytometry. We found IgM to be essential in AHR but not Th2 airway inflammation or eosinophilia. RNA sequencing of lung tissue suggested that IgM regulated AHR through modulating brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1) and other genes. Deletion of BAIAP2L1 led to a differential reduction in human ASM contraction when stimulated with TNF-alpha and acetylcholine, but not IL-13. 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Deletion of BAIAP2L1 led to a differential reduction in human ASM contraction when stimulated with TNF-alpha and acetylcholine, but not IL-13. 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