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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Inhibition of interleukin-17 promotes differentiation of CD25- cells into stable T regulatory cells in patients with autoimmune hepatitis
Gastroenterology, Volume 142, No. 7, Year 2012
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Description
Background & Aims: Patients with autoimmune hepatitis (AIH) have reduced numbers and function of CD4+CD25highFOXP3 + 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 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. 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-1β. Conclusions: Blocking Th17 allows ngTregs to differentiate into functionally stable immune inhibitory cells; this approach might be developed for therapy of patients with AIH. © 2012 AGA Institute.
Authors & Co-Authors
Liberal, Rodrigo
United Kingdom, London
King's College Hospital
Holder, Beth
United Kingdom, London
King's College Hospital
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Ma, Yun
United Kingdom, London
King's College Hospital
Mieli- Vergani, Giorgina
United Kingdom, London
King's College Hospital
Statistics
Citations: 93
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1053/j.gastro.2012.02.041
ISSN:
00165085
Research Areas
Infectious Diseases