In:
The Journal of Immunology, The American Association of Immunologists, Vol. 210, No. 1_Supplement ( 2023-05-01), p. 79.09-79.09
Abstract:
Inflammatory bowel disease (IBD) is a complex inflammatory disease, for which few effective therapies exist. The goal of our current work was to show: i) that such a complex, immune cell-driven pathogenesis could be captured on Emulate’s human Colon Intestine-Chips; and ii) that this could be used as a novel human-centric system to support IBD drug development including anti-TNF-α antibodies. Methods: PBMCs were perfused through the vascular (bottom) channel in untreated ‘resting’ or cytokine-‘primed’ Colon Intestine-Chips. Clinically relevant IBD drugs, including anti-TNF-α antibodies (Humira and Cimzia), as well as dexamethasone and AJM300 were administered through the vascular channel during PBMC administration. Total cell recruitment, effluent biomarker secretion (cytokines, calprotectin, C-reactive protein), and barrier function were analyzed for 72 hours. Results: α4β7 +‘gut-tropic’ PBMCs (monocytes, CD4 +, CD8 +, and NK cells) preferentially adhered and transmigrated in a cytokine priming-dependent manner. These PBMCs released clinically relevant IBD cytokines and biomarkers and induced barrier disruption, a hallmark of IBD. Anti-TNF-α antibodies and AJM300 caused reduced PBMC recruitment, inflammatory response and barrier disruption & gt;90%. Dexamethasone had more modest effects, as expected. Conclusion: The human Colon Intestine-Chip can both model complex immune cell-driven IBD and validate effects of clinically relevant IBD drugs. This system could provide predictive validity for pre-clinical development of new IBD drugs.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.210.Supp.79.09
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2023
detail.hit.zdb_id:
1475085-5
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