Longhi MS et al. – Blocking T–helper (Th)17 allows ngTregs to differentiate into functionally stable immune inhibitory cells; this approach might be developed for therapy of patients with autoimmune hepatitis (AIH).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 β or neutralizing antibodies against IL–6 and IL–1β (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.
- 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–1β.