An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit
Intestinal Inflammation
Barrette Kathleen – Dreesen Erwin
Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F
Background
Inflammatory bowel diseases
- Crohn’s disease- Ulcerative colitis
Inflammatory bowel diseases
- Crohn’s disease- Ulcerative colitis
Inflammatory bowel diseases
- Crohn’s disease- Ulcerative colitis
Murine models
CD45RBhigh CD4+ T-cells
C o l i t i s
CD45RBlow CD4+ T cells
Treg
CD45RBhigh CD4+ T cells
Th1
Immune-suppressive
Immune-stimulative
Question?
The role of IL-10 in IBD?
“Is there evidence that IL-10 plays an important role in mucosal immune regulation?”
IL-10 knock-out mice enterocolitis (Kühn et al. 1993)
rIL-10 administration no colitis in SCID mice restored with CD45RBhigh CD4+ T cells
(Powrie et al. 1994)
CD45RBhigh CD4+ T cells, isolated from transgenic mice that expressed IL-10 under the IL-2 promotor failed to transfer colitis, but rather were able to inhibit colitis induced by WT CD45RBhigh CD4+ T cells
(Hagenbaugh et al. 1997)
Experimental evidence?
IL-10-/- mice Treg?
Treatment with anti-IL-10(R) mAb colitis?
Colitis T1h cells secreting IFN-g and TNF-a in the lesions
IL-10-/- mice Treg?
Treatment with anti-IL-10(R) mAb colitis?
Colitis T1h cells secreting IFN-g and TNF-a in the lesions
CD45RBhigh CD4+ T-cells
C o l i t i s
C o l i t i s
RAG-2-/- mice
WT
CD45RBhigh CD4+ T-cells
C o l i t i s
C o l i t i s
RAG-2-/- mice
WT
C o l i t i s
W
CD45RBhigh CD4+ T-cellsCD45RBlow CD4+ T-cells
C o l i t i s
RAG-2-/- mice
C o l i t i s
W
CD45RBlow CD4+ T-cells
IL-10-/- WT
CD45RBhigh CD4+ T-cells
C o l i t i s
RAG-2-/- mice
C o l i t i s
W
CD45RBlow CD4+ T-cells
IL-10-/-