| Literature Basic Information |
| Title | Inhibition of interleukin-17 promotes differentiation of CD25? cells into stable T regulatory cells in patients with autoimmune hepatitis. |
| Author | Longhi MS, Liberal R, Holder B, Robson SC, Ma Y, Mieli-Vergani G, Vergani D. |
| Journal | Gastroenterology. |
| PMID | 22387392 |
| Publication date | 2012 |
| Abstract |
| BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) have reduced numbers and function of CD4+CD25(high)FOXP3+ T regulatory cells (Tregs). Tregs can be generated from CD25? (ngTreg) cells, which suppress the immune response less efficiently than Tregs. We investigated whether their differentiation into T-helper (Th)17 cells, an effector subset that has the same CD4+ progenitors as Tregs, accounts for the reduced suppressive functions of ngTregs. We investigated whether blocking interleukin (IL)-17 increased the immunosuppressive activity of Tregs. METHODS:ngTregs were generated from 36 patients with AIH and 23 healthy subjects (controls). During Treg differentiation, expression of IL-17 was inhibited by physical removal of IL-17-secreting cells, exposure to recombinant transforming growth factor ?? or neutralizing antibodies against IL-6 and IL-1?? (to promote differentiation of ngTregs vs Th17 cells), small inhibitory RNAs specific for the Th17 transcription factor RORC, or a combination of all these approaches. RESULTS: ngTregs from patients with AIH contained greater proportions of IL-17+ and RORC+ cells than Tregs from controls. All approaches to inhibit IL-17 increased expression of FOXP3 by ngTregs and their suppressive functions. Inhibition of IL-17 led to development of ngTregs that were phenotypically stable and did not acquire proinflammatory properties after exposure to IL-6 and IL-1??. CONCLUSIONS: Blocking Th17 allows ngTregs to differentiate into functionally stable immune inhibitory cells; this approach might be developed for therapy of patients with AIH. |
| Literature Indexing Information |
| Study Type | Observation Study |
| Relating Record | D2G000342Pr2518900 |
| D2G000342Ge00946100 |
| D2G000342Pr2523500 |
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| Index Term | |
