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RETRACTED: X-Linked Immunodeficient Mice With No Functional Bruton's Tyrosine Kinase Are Protected From Sepsis-Induced Multiple Organ Failure.

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Title: RETRACTED: X-Linked Immunodeficient Mice With No Functional Bruton's Tyrosine Kinase Are Protected From Sepsis-Induced Multiple Organ Failure.
Authors: O'Riordan, Caroline E., Purvis, Gareth S. D., Collotta, Debora, Krieg, Nadine, Wissuwa, Bianka, Sheikh, Madeeha H., Ferreira Alves, Gustavo, Mohammad, Shireen, Callender, Lauren A., Coldewey, Sina M., Collino, Massimo, Greaves, David R., Thiemermann, Christoph
Source: Frontiers in Immunology; 2025, p1-20, 20p
Subject Terms: BRUTON tyrosine kinase, MULTIPLE organ failure, CYTOKINE release syndrome, BACTERIAL diseases, NLRP3 protein
Abstract: We previously reported the Bruton's tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis. Now we show that genetic deficiency of the BTK gene alone in Xid mice confers protection against cardiac, renal, and liver injury in polymicrobial sepsis and reduces hyperimmune stimulation ("cytokine storm") induced by an overwhelming bacterial infection. Protection is due in part to enhanced bacterial phagocytosis in vivo , changes in lipid metabolism and decreased activation of NF-κB and the NLRP3 inflammasome. The inactivation of BTK leads to reduced innate immune cell recruitment and a phenotypic switch from M1 to M2 macrophages, aiding in the resolution of sepsis. We have also found that BTK expression in humans is increased in the blood of septic non-survivors, while lower expression is associated with survival from sepsis. Importantly no further reduction in organ damage, cytokine production, or changes in plasma metabolites is seen in Xid mice treated with the BTK inhibitor ibrutinib, demonstrating that the protective effects of BTK inhibitors in polymicrobial sepsis are mediated solely by inhibition of BTK and not by off-target effects of this class of drugs. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
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  Label: Title
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  Data: RETRACTED: X-Linked Immunodeficient Mice With No Functional Bruton's Tyrosine Kinase Are Protected From Sepsis-Induced Multiple Organ Failure.
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  Data: <searchLink fieldCode="AR" term="%22O'Riordan%2C+Caroline+E%2E%22">O'Riordan, Caroline E.</searchLink><br /><searchLink fieldCode="AR" term="%22Purvis%2C+Gareth+S%2E+D%2E%22">Purvis, Gareth S. D.</searchLink><br /><searchLink fieldCode="AR" term="%22Collotta%2C+Debora%22">Collotta, Debora</searchLink><br /><searchLink fieldCode="AR" term="%22Krieg%2C+Nadine%22">Krieg, Nadine</searchLink><br /><searchLink fieldCode="AR" term="%22Wissuwa%2C+Bianka%22">Wissuwa, Bianka</searchLink><br /><searchLink fieldCode="AR" term="%22Sheikh%2C+Madeeha+H%2E%22">Sheikh, Madeeha H.</searchLink><br /><searchLink fieldCode="AR" term="%22Ferreira+Alves%2C+Gustavo%22">Ferreira Alves, Gustavo</searchLink><br /><searchLink fieldCode="AR" term="%22Mohammad%2C+Shireen%22">Mohammad, Shireen</searchLink><br /><searchLink fieldCode="AR" term="%22Callender%2C+Lauren+A%2E%22">Callender, Lauren A.</searchLink><br /><searchLink fieldCode="AR" term="%22Coldewey%2C+Sina+M%2E%22">Coldewey, Sina M.</searchLink><br /><searchLink fieldCode="AR" term="%22Collino%2C+Massimo%22">Collino, Massimo</searchLink><br /><searchLink fieldCode="AR" term="%22Greaves%2C+David+R%2E%22">Greaves, David R.</searchLink><br /><searchLink fieldCode="AR" term="%22Thiemermann%2C+Christoph%22">Thiemermann, Christoph</searchLink>
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  Data: Frontiers in Immunology; 2025, p1-20, 20p
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  Data: <searchLink fieldCode="DE" term="%22BRUTON+tyrosine+kinase%22">BRUTON tyrosine kinase</searchLink><br /><searchLink fieldCode="DE" term="%22MULTIPLE+organ+failure%22">MULTIPLE organ failure</searchLink><br /><searchLink fieldCode="DE" term="%22CYTOKINE+release+syndrome%22">CYTOKINE release syndrome</searchLink><br /><searchLink fieldCode="DE" term="%22BACTERIAL+diseases%22">BACTERIAL diseases</searchLink><br /><searchLink fieldCode="DE" term="%22NLRP3+protein%22">NLRP3 protein</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: We previously reported the Bruton's tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis. Now we show that genetic deficiency of the BTK gene alone in Xid mice confers protection against cardiac, renal, and liver injury in polymicrobial sepsis and reduces hyperimmune stimulation ("cytokine storm") induced by an overwhelming bacterial infection. Protection is due in part to enhanced bacterial phagocytosis in vivo , changes in lipid metabolism and decreased activation of NF-κB and the NLRP3 inflammasome. The inactivation of BTK leads to reduced innate immune cell recruitment and a phenotypic switch from M1 to M2 macrophages, aiding in the resolution of sepsis. We have also found that BTK expression in humans is increased in the blood of septic non-survivors, while lower expression is associated with survival from sepsis. Importantly no further reduction in organ damage, cytokine production, or changes in plasma metabolites is seen in Xid mice treated with the BTK inhibitor ibrutinib, demonstrating that the protective effects of BTK inhibitors in polymicrobial sepsis are mediated solely by inhibition of BTK and not by off-target effects of this class of drugs. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3389/fimmu.2020.581758
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        Text: English
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      – SubjectFull: BRUTON tyrosine kinase
        Type: general
      – SubjectFull: MULTIPLE organ failure
        Type: general
      – SubjectFull: CYTOKINE release syndrome
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      – SubjectFull: BACTERIAL diseases
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      – SubjectFull: NLRP3 protein
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              Text: 2025
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