CPB 697 RESEARCH SEMINAR

DEPARTMENT OF COMPARATIVE PATHOBIOLOGY

Seung Goo Kang, MS

Graduate Student in Immunology

Department of Comparative Pathobiology

Purdue University

“Alteration Of The Mouse Gut Chemokine Network In Chronic Spontaneous Inflammation

And Its Impact On Migration Of T Cell Subsets”

Thursday, November 9, 2006

VPTH 112

3:30 p.m.

ABSTRACT:

It has been unclear which chemoattractant system is involved in migration of T cell subsets to chronically inflamed lesions of the intestine. SAMP1/YP mice develop a spontaneous chronic transmural intestinal lesion specifically in the ileum. Using these mice, we investigated the gut chemokine network involved in specific migration of T cell subsets to the inflamed lesion of the intestine. We performed extensive studies to identify a gut chemokine network induced in intestinal inflammation and to determine gut T cell expression of chemokine receptors and the role of the chemokine network in migration of conventional and FoxP3⁺ suppressor T cells and intestinal inflammation. Results: The expression of homeostatic chemokines is largely unchanged in the inflamed lesion of SAMP1/YP mice compared to control mice. However, an additional chemokine axis (CCL5-CCR5) was up-regulated in the inflamed intestine of SAMP1/YP mice compared to control mice. Activated T cells from SAMP1/YP mice compared to control mice were hyper-responsive to CCL5 in chemotaxis. CCR5⁺ T cells preferentially migrate to the inflamed lesion but not to the healthy intestine, which can be blocked by a CCR5 antagonist. Interestingly, many more FoxP3⁺, than FoxP3^-, T cells of the inflamed lesion of SAMP1/YP mice expressed CCR5. CCR5 blockade suppressed the migration of FoxP3⁺ T cells into inflamed intestine and significantly exacerbated the intestinal inflammation. The inflammation-related CCL5-CCR5 chemokine-network, induced on top of the homeostatic chemokine network in the intestinal lesion, is involved in recruitment of FoxP3⁺ T cells and is, actually, beneficial.