IL-7 is essential for the development and the persistence of chronic colitis

Although IL-7 has recently emerged as a key cytokine involved in controlling the homeostatic turnover and the survival of peripheral resting memory CD4⁺ T cells, its potential to be sustained pathogenic CD4⁺ T cells in chronic immune diseases, such as inflammatory bowel diseases, still remains unclear. In this study, we demonstrate that IL-7 is essential for the development and the persistence of chronic colitis induced by adoptive transfer of normal CD4⁺CD45RB^high T cells or colitogeoic lamina propria (LP) CD4⁺ memory T cells into immunodeficient IL-7^+/+ x RAG-1^-/- and IL-7^-/- x RAG-1^-/- mice. Although EL-7^+/+ x RAG-1^-/- recipients transferred-with CD4⁺CD45RB^high splenocytes developed massive inflammation of the large intestinal mucosa concurrent with massive expansion of Th1 cells, IL-7^-/- x RAG-1^-/- recipients did not. Furthermore, IL-7^-/- x RAG-1^-/-, but not IL-7^+/+ x RAG-1^-/-, mice transferred with LP CD4 ⁺CD44^highCD62L^-IL-7Rα^high effector-memory T cells (T_EM) isolated from colitic CD4 ⁺CD45RB^high-transferred mice did not develop colitis. Although rapid proliferation of transferred colitogenic LP CD4⁺ T_EM cells was observed in the in IL-7^-/- x RAG-1 ^-/- mice to a similar extent of those in IL-7^-/- x RAG-1^-/- mice, Bcl-2 expression was significantly down-modulated in the transferred CD4⁺ T cells in IL-7^-/- x RAG-1 ^-/- mice compared with those in IL-7^+/+ x RAG-1 ^-/- mice. Taken together, IL-7 is essential for the development and the persistence of chronic colitis as a critical survival factor for colitogenic CD⁺ T_EM cells, suggesting that therapeutic approaches targeting IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases.