| First Author | Kermarrec L | Year | 2019 |
| Journal | Br J Pharmacol | Volume | 176 |
| Issue | 9 | Pages | 1235-1250 |
| PubMed ID | 30736100 | Mgi Jnum | J:280279 |
| Mgi Id | MGI:6359052 | Doi | 10.1111/bph.14614 |
| Citation | Kermarrec L, et al. (2019) Semaphorin-3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C(+) and CD4(+) CD25(-) T-cells. Br J Pharmacol 176(9):1235-1250 |
| abstractText | BACKGROUND AND PURPOSE: An alteration in the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin-3E (SEMA3E), a secreted guidance protein, regulates various immune responses. EXPERIMENTAL APPROACH: We investigated the expression of SEMA3E in colonic biopsies of active UC patients and its mechanisms in Sema3e(-/-) mice using an experimental model of UC. KEY RESULTS: SEMA3E level was decreased in active UC patients and negatively correlated with pro-inflammatory mediators. Colonic expression of SEMA3E was reduced in colitic Sema3e(+/+) mice, and recombinant (rec-) Plexin-D1 treatment exacerbated disease severity. In vivo rec-SEMA3E treatment restored SEMA3E level in colitic Sema3e(+/+) mice. In Sema3e(-/-) mice, disease severity was increased, and rec-SEMA3E ameliorated these effects. Lack of Sema3e increased the expression of CD11c and CD86 markers. Colitic Sema3e(-/-) splenocytes and splenic CD11c(+) cells produced more IL-12/23 and IFN-gamma compared to Sema3e(+/+) , and rec-SEMA3E reduced their release as much as NF-kappaB inhibitors, whereas an NF-kappaB activator increased their production and attenuated the effect of rec-SEMA3E. Colitic Sema3e(-/-) splenic CD11c(+) /CD4(+) CD25(-) T-cell co-cultures produced higher concentrations of IFN-gamma and IL-17 when compared to colitic Sema3e(+/+) splenic cell co-cultures, and rec-SEMA3E decreased these effects. In vitro, anti-IL-12p19 and -12p35 antibodies and rec-IL-12 and -23 treatment confirmed the crosstalk between CD11c(+) and CD4(+) CD25(-) T-cells. CONCLUSION AND IMPLICATIONS: SEMA3E is reduced in colitis and modulates colonic inflammation by regulating the interaction between CD11c(+) and CD4(+) CD25(-) T-cells via an NF-kappaB-dependent mechanism. Thus, SEMA3E could be a potential therapeutic target for UC patients. |
