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| Content Provider | PubMed Central |
|---|---|
| Author | Nalle, Sam C. Kwak, H. Aimee Edelblum, Karen L. Joseph, Nora E. Singh, Gurminder Khramtsova, Galina F. Mortenson, Eric D. Savage, Peter A. Turner, Jerrold R. |
| Abstract | Previous studies have shown a correlation between pre-transplant conditioning intensity, intestinal barrier loss, and graft-versus-host disease (GVHD) severity. However, since irradiation and other forms of pre-transplant conditioning have pleiotropic effects, the precise role of intestinal barrier loss in GVHD pathogenesis remains unclear. We developed GVHD models that allowed us to isolate the specific contributions of distinct pre-transplant variables. First, intestinal damage was required for the induction of minor mismatch (MHC-matched) GVHD, but was not necessary for major mismatch GVHD, demonstrating fundamental pathogenic distinctions between these forms of disease. Moreover, recipient NK cells prevented minor mismatch GVHD by limiting expansion and target organ infiltration of alloreactive T cells via a perforin-dependent mechanism, revealing a previously unrecognized immunoregulatory function of recipient NK cells in GVHD. Minor mismatch GVHD required MyD88-mediated TLR4 signaling on donor cells, and intestinal damage could be bypassed by parenteral LPS administration, indicating a critical role for the influx of bacterial components triggered by intestinal barrier loss. In all, the data demonstrate that pre-transplant conditioning plays a dual role in promoting minor mismatch GVHD by both depleting recipient NK cells and inducing intestinal barrier loss. |
| Related Links | http://dx.doi.org/10.1126/scitranslmed.3008941 |
| Starting Page | 24387 |
| File Format | |
| ISSN | 19466234 |
| e-ISSN | 19466242 |
| Journal | Science translational medicine |
| Issue Number | 243 |
| Volume Number | 6 |
| Language | English |
| Publisher Date | 2014-07-02 |
| Access Restriction | Open |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
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