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T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS

Author

Listed:
  • Tasuku Kawano

    (The University of Illinois at Urbana-Champaign
    Tohoku Medical and Pharmaceutical University)

  • Jinyan Zhou

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign)

  • Shehata Anwar

    (The University of Illinois at Urbana-Champaign
    Beni-Suef University (BSU))

  • Haneen Salah

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign)

  • Andrea H. Dayal

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign)

  • Yuzuki Ishikawa

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign)

  • Katelyn Boetel

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign)

  • Tomoko Takahashi

    (Tohoku Medical and Pharmaceutical University)

  • Kamal Sharma

    (University of Illinois, Chicago)

  • Makoto Inoue

    (The University of Illinois at Urbana-Champaign
    The University of Illinois at Urbana-Champaign
    Beckman Institute for Advanced Science and Technology)

Abstract

Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is a condition frequently occurring in immunocompromised patients receiving antiretroviral therapy. C-IRIS patients exhibit many critical symptoms, including pulmonary distress, potentially complicating the progression and recovery from this condition. Here, utilizing our previously established mouse model of unmasking C-IRIS (CnH99 preinfection and adoptive transfer of CD4+ T cells), we demonstrated that pulmonary dysfunction associated with the C-IRIS condition in mice could be attributed to the infiltration of CD4+ T cells into the brain via the CCL8-CCR5 axis, which triggers the nucleus tractus solitarius (NTS) neuronal damage and neuronal disconnection via upregulated ephrin B3 and semaphorin 6B in CD4+ T cells. Our findings provide unique insight into the mechanism behind pulmonary dysfunction in C-IRIS and nominate potential therapeutic targets for treatment.

Suggested Citation

  • Tasuku Kawano & Jinyan Zhou & Shehata Anwar & Haneen Salah & Andrea H. Dayal & Yuzuki Ishikawa & Katelyn Boetel & Tomoko Takahashi & Kamal Sharma & Makoto Inoue, 2023. "T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39518-x
    DOI: 10.1038/s41467-023-39518-x
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    References listed on IDEAS

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    1. Ken-ichiro Nakajima & Zhenzhong Cui & Chia Li & Jaroslawna Meister & Yinghong Cui & Ou Fu & Adam S. Smith & Shalini Jain & Bradford B. Lowell & Michael J. Krashes & Jürgen Wess, 2016. "Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
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