B cell-intrinsic Ssu72 phosphatase is a key regulator of allergic asthma
- 1Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
- 2Department of Immunology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
- 3Personalized Cancer Immunotherapy Research Center, Sungkyunkwan University, Suwon, Republic of Korea
Abstract
B cell-derived immunoglobulin E (IgE) plays a crucial role in the development of allergic asthma. However, the intrinsic regulation of B cell function in this context is not fully understood. Here we investigated the role of Ssu72 phosphatase expressed in B cells during house dust mite (HDM)-induced asthma. Ssu72 expression was significantly increased in B cells stimulated with anti-CD40 and IL-4, as well as in B cells infiltrating the lungs of HDM-induced asthmatic mice. Notably, mice with B cell-specific deletion of Ssu72 exhibited considerably milder lung inflammation and lower serum levels of IgG1 and IgE compared to wild-type mice in HDM-induced asthma. In addition, the absence of Ssu72 in B cells resulted in a reduction in the number of IgG1- and IgE class-switched B cells and a decrease in soluble CD23 production, which correlated with lower expression of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and matrix metalloproteinase 9 (MMP9). Mechanistically, our findings suggest that Ssu72 deficiency may dysregulate the AMPK–mTORC1 balance through hyperphosphorylation of AMPKα. In adoptive transfer experiments, Ssu72-deficient B cells were less effective than wild-type B cells in promoting the effector phase of HDM-induced asthma in B cell-deficient hosts following HDM sensitization. Furthermore, B cell-specific deletion of Ssu72 led to the reduced production of IL-4 and IL-13 by CD4⁺ T cells and diminished MHC class II upregulation in lymph nodes and lung B cells during HDM-induced asthma. These findings identify B cell Ssu72 as a crucial regulator of B cell activation and function in allergic asthma.
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BibTeX
@article{koo2026cellintrinsic,
title = {{B cell-intrinsic Ssu72 phosphatase is a key regulator of allergic asthma}},
author = {Seo-Young Koo and Naiyu Wang and Min-Hee Kim and Sujin Lee and Tae Jin Kim and Chang-Woo Lee},
journal = {Experimental \& Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1038/s12276-026-01859-0},
url = {https://doi.org/10.1038/s12276-026-01859-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - B cell-intrinsic Ssu72 phosphatase is a key regulator of allergic asthma
AU - Seo-Young Koo
AU - Naiyu Wang
AU - Min-Hee Kim
AU - Sujin Lee
AU - Tae Jin Kim
AU - Chang-Woo Lee
PY - 2026
DA - 2026/10/05
JO - Experimental & Molecular Medicine
DO - 10.1038/s12276-026-01859-0
UR - https://doi.org/10.1038/s12276-026-01859-0
AB - B cell-derived immunoglobulin E (IgE) plays a crucial role in the development of allergic asthma. However, the intrinsic regulation of B cell function in this context is not fully understood. Here we investigated the role of Ssu72 phosphatase expressed in B cells during house dust mite (HDM)-induced asthma. Ssu72 expression was significantly increased in B cells stimulated with anti-CD40 and IL-4, as well as in B cells infiltrating the lungs of HDM-induced asthmatic mice. Notably, mice with B cell-specific deletion of Ssu72 exhibited considerably milder lung inflammation and lower serum levels of IgG1 and IgE compared to wild-type mice in HDM-induced asthma. In addition, the absence of Ssu72 in B cells resulted in a reduction in the number of IgG1- and IgE class-switched B cells and a decrease in soluble CD23 production, which correlated with lower expression of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and matrix metalloproteinase 9 (MMP9). Mechanistically, our findings suggest that Ssu72 deficiency may dysregulate the AMPK–mTORC1 balance through hyperphosphorylation of AMPKα. In adoptive transfer experiments, Ssu72-deficient B cells were less effective than wild-type B cells in promoting the effector phase of HDM-induced asthma in B cell-deficient hosts following HDM sensitization. Furthermore, B cell-specific deletion of Ssu72 led to the reduced production of IL-4 and IL-13 by CD4⁺ T cells and diminished MHC class II upregulation in lymph nodes and lung B cells during HDM-induced asthma. These findings identify B cell Ssu72 as a crucial regulator of B cell activation and function in allergic asthma.
SN - 1226-3613
SN - 2092-6413
ER -