Inhibition of Interleukin-17 Promotes Differentiation of CD25-Cells Into Stable T Regulatory Cells in Patients With Autoimmune Hepatitis
Gastroenterology, 06/12/2012Longhi 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).
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.
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