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-/-