Journal article
Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease
Cell reports (Cambridge), Vol.37(13), 110170
12/2021
DOI: 10.1016/j.celrep.2021.110170
PMCID: PMC8759344
PMID: 34965439
Abstract
Osteopontin (OPN) has been considered a potential biomarker of graft-versus-host disease (GVHD). However, the function of OPN in GVHD is still elusive. Using a mouse model of acute GVHD (aGVHD), we report that OPN generated by CD4+ T cells is sufficient to exert a beneficial effect in controlling aGVHD through limiting gastrointestinal pathology, a major target organ of aGVHD. CD4+ T cell-derived OPN works on CD44 expressed in intestinal epithelial cells (IECs) and abates cell death of IECs. OPN also modulates gut microbiota with enhanced health-associated commensal bacteria Akkermansia. Importantly, we use our in vivo mouse mutant model to specifically express OPN isoforms and demonstrate that secreted OPN (sOPN), not intracellular OPN (iOPN), is solely responsible for the protective role of OPN. This study demonstrates that sOPN generated by CD4+ T cells is potent enough to limit aGVHD.
Details
- Title: Subtitle
- Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease
- Creators
- Nupur AggarwalM. Elizabeth DeerhakeDevon DiPalmaShailesh K ShahiMargaret R GaggioliAshutosh K MangalamMari L Shinohara
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.37(13), 110170
- DOI
- 10.1016/j.celrep.2021.110170
- PMID
- 34965439
- PMCID
- PMC8759344
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: F30-AI140497, R01-AI08810
- Language
- English
- Date published
- 12/2021
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984204116302771
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