Thread by @Cori_Fain

🚨 Alert! We are excited to share our new preprint in which we define the roles of individual class I molecules on brain endothelium in the regulation of T cell responses and development of neuropathology in experimental cerebral malaria
biorxiv.org/content/10.110…

CD8 T cell engagement of brain vasculature has been implicated in the neuropathology of cerebral malaria. In this work we interrogated human and mouse data during infection and noted upregulation of activation and Ag-presentation molecules or transcripts in brain endothelium

When either class I was ablated, the mice were normal at baseline and also established normal peripheral plasmodium infection and peripheral immune responses. However, T cell interactions with brain endothelium were disrupted during infection

CD8 T cell infiltration into brain was differentially regulated by H-2Kb and H-2Db, however, infiltration of CD8s producing IFNy was comparable, and ablation of either class I resulted in decreased infiltration of activated Ag-specific CD8s, specifically into brain parenchyma

Blood-brain barrier disruption and vascular leakage were dependent upon the presence of either H-2Kb or H-2Db on brain endothelium and resulted in differential patterns of leakage throughout the brain. Deletion of class I from brain vasculature protected from this pathology

We performed parabiosis, joining Db Cre- Littermates to endothelial specific Db cKO mice and confirmed that peripheral immunity was not impeded and that changes in pathology are truly barrier and brain-specific, and dependent upon class I antigen presentation by brain endothelium

We describe how each class I molecule differentially regulates cell death and neuroinflammation during ECM. Kb restriction supported neuronal cell death, Db restriction supported endothelial and neuronal cell death. cKOs rescued cell death, resulting in survival of the animals!!!

I would like to thank everyone involved in this work @DrAaronJJohnson lab and @LongJun_Wu @FionaJiaying @KAyasoufi @Yue_Wu_IMM @AbigailDropik @wolf_delaney @ZackAibaidula @ZachariahTritz @EppingLecia @StinaUrbanPhD @HartyLab @IanParneyMDPhD @Jie_Immunology and twitterless

@MayoGradSchool @MayoClinicNeuro @MayoClinic @NeuroImmunology @NeuroPaperBot @womeninstemSA @WorldWomenNeuro @Women_inNeuro @SfNtweets @MESAmalaria @womeninmalaria @MalariaPapers @malariapreprint @endothelialnews @bbbpapers @500womensci @mothersinsci @preprintclub

#tweetorial #bbb #neuroimmunology #cerebralmalaria #NativeinSTEM #WomenInNeuroIMM #NSPeeps #NINDSFellow #WomenInSTEM #WomeninScience #NeuroScholar #womeninneuroscience #scicomm
For more information his work will be presented at #SfN2022, contact @Cori_Fain or [e-mail]