| First Author | Willemze RA | Year | 2019 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 317 |
| Issue | 5 | Pages | G557-G568 |
| PubMed ID | 31322912 | Mgi Jnum | J:311700 |
| Mgi Id | MGI:6710651 | Doi | 10.1152/ajpgi.00067.2019 |
| Citation | Willemze RA, et al. (2019) Acetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis. Am J Physiol Gastrointest Liver Physiol 317(5):G557-G568 |
| abstractText | Clinical trials suggest that vagus nerve stimulation presents an alternative approach to classical immune suppression in Crohn's disease. T cells capable of producing acetylcholine (ChAT(+) T cells) in the spleen are essential mediators of the anti-inflammatory effect of vagus nerve stimulation. Besides the spleen, ChAT(+) T cells are found abundantly in Peyer's patches of the small intestine. However, the role of ChAT(+) T cells in colitis pathogenesis is unknown. Here, we made use of CD4(cre)ChAT(fl/fl) mice (CD4ChAT(-/-) mice) lacking ChAT expression specifically in CD4(+) T cells. Littermates (ChAT(fl/fl) mice) served as controls. In acute dextran sulfate sodium (DSS)-induced colitis (7 days of 2% DSS in drinking water), CD4ChAT(-/-) mice showed attenuated colitis and lower intestinal inflammatory cytokine levels compared with ChAT(fl/fl) mice. In contrast, in a resolution model of DSS-induced colitis (5 days of 2% DSS followed by 7 days without DSS), CD4ChAT(-/-) mice demonstrated a worsened colitis recovery and augmented colonic histological inflammation scores and inflammatory cytokine levels as compared with ChAT(fl/fl) mice. In a transfer colitis model using CD4(+)CD45RB(high) T cells, T cells from CD4ChAT(-/-) mice induced a similar level of colitis compared with ChAT(fl/fl) T cells. Together, our results indicate that ChAT(+) T cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, whereas they are supporting the later resolution process of this innate immune-driven colitis. Surprisingly, ChAT expression in T cells seems redundant in the context of T cell-driven colitis.NEW & NOTEWORTHY By using different mouse models of experimental colitis, we provide evidence that in dextran sulfate sodium-induced colitis, ChAT(+) T cells capable of producing acetylcholine worsen the acute immune response, whereas they support the later healing phase of this innate immune-driven colitis. |
