Blood Res.  2023 Jun;58(2):105-111. 10.5045/br.2023.2022238.

Overexpression of S100A9 in donor T cells is associated with reconstitution of gut microbiota and outcome of allogeneic hematopoietic stem cell transplantation

• Kim S
• Lim S
• Razmkhah F
• Choi J

• KMID: 2543951
• DOI: http://doi.org/10.5045/br.2023.2022238

Figure

• 

  Fig. 1 Ifngr1-/- and S100a9-overexpressing donor T cells alter intestinal microbiota composition after allo-HSCT. Allo-HSCT was performed as follows; 5×106 TCD-BM (CD45.1+ WT) and 5×105 T cells (CD45.2+ WT, Ifngr1-/- and S100a9 Tg) obtained from B6 mice were transplanted into lethally irradiated (900 cGy) Balb/c allogeneic recipient mice. TCD-BM only group serves as no GvHD control. The abundance of fecal microbiota at different taxonomic levels was measured by 16S rRNA sequencing; (A) phylum, (B) family, (C) genus, and (D) species. The bar graph displayed only the top 10 most abundant operational taxonomic units (OTUs) on day 0 (left panels) and day 7 (middle panels) after allo-HSCT. Ternary plots showing the distribution of the top 10 most abundant OTUs on day 7 (right panels). All error bars are represented as mean±standard deviation.

• 

  Fig. 2 Intestinal microbial community at the species level after allo-HSCT. Heat map analysis showing the abundance of the fecal microbiota at the level of species (>0.01%, top 25) in WT, Ifngr1-/-, and S100a9 Tg T cells transplanted recipient mice. The heat map was generated using the Heatmapper online software (http://www2.heatmapper.ca/expression/). The hierarchical clustering was performed using the Euclidean metric and complete linkage.

Reference

1. Scott AP, Thirunavukarasu C, Kennedy GA, Tey SK. 2020; Favourable survival in "Discordant" acute gastrointestinal graft versus host disease (GI-GVHD) is explained by mild clinical course and treatment-responsive disease. Int J Hematol. 111:574–8. DOI: 10.1007/s12185-019-02813-9. PMID: 31912373.

2. van Lier YF, Davids M, Haverkate NJE, et al. 2020; Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med. 12:eaaz8926. DOI: 10.1126/scitranslmed.aaz8926. PMID: 32801142.

3. Weber D, Oefner PJ, Dettmer K, et al. 2016; Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. Bone Marrow Transplant. 51:1087–92. DOI: 10.1038/bmt.2016.66. PMID: 26999466.

4. Payen M, Nicolis I, Robin M, et al. 2020; Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity. Blood Adv. 4:1824–32. DOI: 10.1182/bloodadvances.2020001531. PMID: 32353108. PMCID: PMC7218439.

5. Jenq RR, Ubeda C, Taur Y, et al. 2012; Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 209:903–11. DOI: 10.1084/jem.20112408. PMID: 22547653. PMCID: PMC3348096.

6. Stein-Thoeringer CK, Nichols KB, Lazrak A, et al. 2019; Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 366:1143–9. DOI: 10.1126/science.aax3760. PMID: 31780560. PMCID: PMC7003985.

7. Choi J, Ziga ED, Ritchey J, et al. 2012; IFNγR signaling mediates alloreactive T-cell trafficking and GVHD. Blood. 120:4093–103. DOI: 10.1182/blood-2012-01-403196. PMID: 22972985. PMCID: PMC3496960.

8. Choi J, Cooper ML, Staser K, et al. 2018; Baricitinib-induced blockade of interferon gamma receptor and interleukin-6 receptor for the prevention and treatment of graft-versus-host disease. Leukemia. 32:2483–94. DOI: 10.1038/s41375-018-0123-z. PMID: 29691471. PMCID: PMC6168427.

9. Kim S, Ashami K, Lim S, et al. 2022; Baricitinib prevents GvHD by increasing Tregs via JAK3 and treats established GvHD by promoting intestinal tissue repair via EGFR. Leukemia. 36:292–5. DOI: 10.1038/s41375-021-01360-9. PMID: 34304247. PMCID: PMC8732299.

10. Kim S, Lim S, Kim B, et al. 2023; S100A9 upregulated by IFNGR signaling blockade functions as a novel GVHD suppressor without compromising GvL in mice. Blood. 141:945–50. DOI: 10.1182/blood.2021012687. PMID: 36477272.

11. Lindenberg F, Krych L, Fielden J, et al. 2019; Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum. Sci Rep. 9:12674. DOI: 10.1038/s41598-019-49081-5. PMID: 31481726. PMCID: PMC6722064.

12. Mathewson ND, Jenq R, Mathew AV, et al. 2016; Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 17:505–13. DOI: 10.1038/ni.3400. PMID: 26998764. PMCID: PMC4836986.

13. Han L, Jin H, Zhou L, et al. 2018; Intestinal microbiota at engraftment influence acute graft-versus-host disease via the Treg/Th17 balance in allo-HSCT recipients. Front Immunol. 9:669. DOI: 10.3389/fimmu.2018.00669. PMID: 29740427. PMCID: PMC5928130. PMID: 12a2fb836d1941459834b909691b621d.

14. Chelakkot C, Choi Y, Kim DK, et al. 2018; Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med. 50:e450. DOI: 10.1038/emm.2017.282. PMID: 29472701. PMCID: PMC5903829.

15. Daquigan N, Seekatz AM, Greathouse KL, Young VB, White JR. 2017; High-resolution profiling of the gut microbiome reveals the extent of Clostridium difficile burden. NPJ Biofilms Microbiomes. 3:35. DOI: 10.1038/s41522-017-0043-0. PMID: 29214047. PMCID: PMC5717231.