| First Author | Tcymbarevich I | Year | 2019 |
| Journal | J Crohns Colitis | Volume | 13 |
| Issue | 2 | Pages | 245-258 |
| PubMed ID | 30535144 | Mgi Jnum | J:295072 |
| Mgi Id | MGI:6459614 | Doi | 10.1093/ecco-jcc/jjy152 |
| Citation | Tcymbarevich I, et al. (2019) Lack of the pH-sensing Receptor TDAG8 [GPR65] in Macrophages Plays a Detrimental Role in Murine Models of Inflammatory Bowel Disease. J Crohns Colitis 13(2):245-258 |
| abstractText | Background: Tissue inflammation in inflammatory bowel diseases [IBD] is associated with local acidification. Genetic variants in the pH-sensing G protein-coupled receptor 65, also known as T cell death-associated gene 8 [TDAG8], have been implicated in IBD and other autoimmune diseases. Since the role of TDAG8 in intestinal inflammation remains unclear, we investigated the function of TDAG8 using murine colitis models. Methods: The effects of TDAG8 deficiency were assessed in dextran sodium sulphate [DSS], IL-10-/-, and T cell transfer colitis murine models. RNA sequencing of acidosis-activated TDAG8-/- and wild-type [WT] peritoneal macrophages [MPhis] was performed. Results: mRNA expression of IFN-gamma, TNF, IL-6, and iNOS in TDAG8-/- mice increased significantly in colonic lymphoid patches and in colonic tissue in acute and chronic DSS colitis, respectively. In transfer colitis, there was a trend towards increased IFN-gamma, iNOS, and IL-6 expression in mice receiving TDAG8-/- T cells. However, absence of TDAG8 did not lead to changes in clinical scores in the models tested. Increased numbers of infiltrating MPhis and neutrophils, but not CD3+ T cells, were observed in DSS-treated TDAG8-/- mice. No differences in infiltrating CD3+ T cells were observed between mice receiving TDAG8-/- or WT naive T cells in transfer colitis. RNA sequencing showed that acidosis activation of TDAG8 in MPhis modulated the expression of immune response genes. Conclusions: TDAG8 deficiency triggers colonic MPhi and neutrophil infiltration, and expression of pro-inflammatory mediators in DSS colitis models. In transfer colitis, mice receiving TDAG8-/- T cells presented a significantly higher spleen weight and a tendency towards increased expression of pro-inflammatory markers of monocyte/MPhi activity. |
