| First Author | Ogrinc Wagner A | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 1 | Pages | e0210998 |
| PubMed ID | 30653608 | Mgi Jnum | J:273272 |
| Mgi Id | MGI:6275873 | Doi | 10.1371/journal.pone.0210998 |
| Citation | Ogrinc Wagner A, et al. (2019) Strain specific maturation of Dendritic cells and production of IL-1beta controls CD40-driven colitis. PLoS One 14(1):e0210998 |
| abstractText | Intestinal integrity is maintained by balanced numbers of CD103+ Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103+ DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe that transgenic mice on a pure Balb/c-background (B/c) do not show any pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon inflammation, without fatal colitis. This graded pathology correlated with the effects of CD40-signalling on DCs in each background, with striking loss of CD103+ DCs in B6, but reduced in F1 and diminished in B/c background. We further show direct correlation of CD103+ DC-numbers with numbers of iTregs, the frequencies of which behave correspondingly. Striking effects on B6-DCs reflected robust loss of surface MHCII, known to be crucial for iTreg induction. Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, support generation of intestinal IFN-gamma+IL-17+ Th17 cells and IFN-gamma+ Th1 cells, responsible for onset of disease. Together, this demonstrates a novel aspect of colitis-control, depending on genetic background. Moreover, strain-specific environmental sensing might alter the CD103+ DC/iTreg-axis to tip intestinal homeostatic balance to pathology. |
