Surviving too long in Crohn's disease

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Figure 1  .

Potential strategies to hamper lymphoaccumulation by targeting defective T cell apoptosis in animal models of Crohn's disease. (A) Interleukin 12 (IL-12), produced by macrophages (M) in response to putative environmental factors, promotes differentiation of Th1 cells, which in turn upregulate macrophage IL-12 synthesis by releasing interferon γ (IFN-γ). Antibodies to IL-12 exert their therapeutic properties by reinduction of T cell apoptosis. (B) Soluble receptor of interleukin 6 (sIL-6R), released by macrophages, may complex with IL-6 and stimulate gp130 on the T cell surface, leading to a STAT-3 dependent cascade of antiapoptotic genes (Bcl-2 and Bcl-x_L) and then to apoptosis resistance. Antibodies to IL-6R prevent this antiapoptotic pathway. (C) Tolerance induction following oral antigen administration may result in T cell production of transforming growth factor β (TGF-β) which mediates apoptotic deletion of T cells thus avoiding lymphoaccumulation.