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

First Author  Kawano T Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  3831
PubMed ID  37380639 Mgi Jnum  J:354867
Mgi Id  MGI:7495149 Doi  10.1038/s41467-023-39518-x
Citation  Kawano T, et al. (2023) T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS. Nat Commun 14(1):3831
abstractText  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.
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