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Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behçet's disease.
Arthritis Res Ther. 2012 May 01; 14(3):R99.AR

Abstract

INTRODUCTION

The purpose of this study was to determine whether anti-tumour necrosis factor alpha (anti-TNF-α) antibody, infliximab, can inhibit T helper 17 (Th17) differentiation in uveitis patients who have Behçet's disease (BD).

METHODS

To measure inflammatory cytokines, ocular fluid samples from BD patients being treated with infliximab were collected. Cluster of differentiation 4 (CD4)+ T cells from BD patients with active uveitis were co-cultured with anti-cluster of differentiation 3/cluster of differentiation 28 (CD3/CD28) antibodies in the presence of infliximab. For the induction of Th17 cells, CD4+ T cells from BD patients were co-cultured with anti-CD3/CD28, anti-interferon-gamma (anti-IFN-γ), anti-interleukin-4 (anti-IL-4), and recombinant proteins such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-23 (IL-23), and TNF-α. The BD T cells were co-cultured with infliximab, and the production of interleukin-17 (IL-17) was evaluated by ELISA and flow cytometry, and the expression of retinoid-acid receptor-related orphan receptor gamma t (RORγt) was also evaluated by flow cytometry. In addition, intraocular cells collected from mice with experimental autoimmune uveitis (EAU) were used for the assay with anti-TNF-α blocking antibody.

RESULTS

Ocular fluids from active uveitis patients who have BD contained significant amounts of inflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-6, and IL-17, while ocular fluids from infliximab patients did not contain any inflammatory cytokines. Activated CD4+ T cells from BD patients produced large amounts of TNF-α and IL-17, whereas T cells in the presence of infliximab failed to produce these cytokines. Polarized Th17 cell lines from BD patients produced large amounts of IL-17, and Th17 cells exposed to infliximab had significantly reduced IL-17 production. Polarized BD Th17 cells expressed large amounts of transcription factor RORγt. In contrast, in vitro-treated infliximab Th17 cells expressed less RORγt. Moreover, intraocular T cells from EAU mice had a high population of IL-17+ cells, and retinal antigen-specific T cells from EAU mice produced large amounts of IL-17 in the presence of retinal peptide. However, the EAU T cells produced less IL-17 if the T cells were treated with anti-TNF-α antibody.

CONCLUSIONS

These results indicate that anti-TNF-α therapy suppresses effector T-cell differentiation in BD patients with uveitis. Thus, suppression of effector T-cell differentiation by anti-TNF-α therapy may provide protection from severe ocular inflammation in BD.

Authors+Show Affiliations

Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. sunaoph@cdb.riken.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22546542

Citation

Sugita, Sunao, et al. "Inhibition of Th17 Differentiation By anti-TNF-alpha Therapy in Uveitis Patients With Behçet's Disease." Arthritis Research & Therapy, vol. 14, no. 3, 2012, pp. R99.
Sugita S, Kawazoe Y, Imai A, et al. Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behçet's disease. Arthritis Res Ther. 2012;14(3):R99.
Sugita, S., Kawazoe, Y., Imai, A., Yamada, Y., Horie, S., & Mochizuki, M. (2012). Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behçet's disease. Arthritis Research & Therapy, 14(3), R99. https://doi.org/10.1186/ar3824
Sugita S, et al. Inhibition of Th17 Differentiation By anti-TNF-alpha Therapy in Uveitis Patients With Behçet's Disease. Arthritis Res Ther. 2012 May 1;14(3):R99. PubMed PMID: 22546542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behçet's disease. AU - Sugita,Sunao, AU - Kawazoe,Yuko, AU - Imai,Ayano, AU - Yamada,Yukiko, AU - Horie,Shintaro, AU - Mochizuki,Manabu, Y1 - 2012/05/01/ PY - 2011/12/19/received PY - 2012/03/15/revised PY - 2012/05/01/accepted PY - 2012/5/2/entrez PY - 2012/5/2/pubmed PY - 2013/5/23/medline SP - R99 EP - R99 JF - Arthritis research & therapy JO - Arthritis Res. Ther. VL - 14 IS - 3 N2 - INTRODUCTION: The purpose of this study was to determine whether anti-tumour necrosis factor alpha (anti-TNF-α) antibody, infliximab, can inhibit T helper 17 (Th17) differentiation in uveitis patients who have Behçet's disease (BD). METHODS: To measure inflammatory cytokines, ocular fluid samples from BD patients being treated with infliximab were collected. Cluster of differentiation 4 (CD4)+ T cells from BD patients with active uveitis were co-cultured with anti-cluster of differentiation 3/cluster of differentiation 28 (CD3/CD28) antibodies in the presence of infliximab. For the induction of Th17 cells, CD4+ T cells from BD patients were co-cultured with anti-CD3/CD28, anti-interferon-gamma (anti-IFN-γ), anti-interleukin-4 (anti-IL-4), and recombinant proteins such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-23 (IL-23), and TNF-α. The BD T cells were co-cultured with infliximab, and the production of interleukin-17 (IL-17) was evaluated by ELISA and flow cytometry, and the expression of retinoid-acid receptor-related orphan receptor gamma t (RORγt) was also evaluated by flow cytometry. In addition, intraocular cells collected from mice with experimental autoimmune uveitis (EAU) were used for the assay with anti-TNF-α blocking antibody. RESULTS: Ocular fluids from active uveitis patients who have BD contained significant amounts of inflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-6, and IL-17, while ocular fluids from infliximab patients did not contain any inflammatory cytokines. Activated CD4+ T cells from BD patients produced large amounts of TNF-α and IL-17, whereas T cells in the presence of infliximab failed to produce these cytokines. Polarized Th17 cell lines from BD patients produced large amounts of IL-17, and Th17 cells exposed to infliximab had significantly reduced IL-17 production. Polarized BD Th17 cells expressed large amounts of transcription factor RORγt. In contrast, in vitro-treated infliximab Th17 cells expressed less RORγt. Moreover, intraocular T cells from EAU mice had a high population of IL-17+ cells, and retinal antigen-specific T cells from EAU mice produced large amounts of IL-17 in the presence of retinal peptide. However, the EAU T cells produced less IL-17 if the T cells were treated with anti-TNF-α antibody. CONCLUSIONS: These results indicate that anti-TNF-α therapy suppresses effector T-cell differentiation in BD patients with uveitis. Thus, suppression of effector T-cell differentiation by anti-TNF-α therapy may provide protection from severe ocular inflammation in BD. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/22546542/Inhibition_of_Th17_differentiation_by_anti_TNF_alpha_therapy_in_uveitis_patients_with_Behçet's_disease_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar3824 DB - PRIME DP - Unbound Medicine ER -