Overexpression of IL-17RC associated with ocular sarcoidosis.

Wenting Wu,Ping Chen,Robert B Nussenblatt,Susan Hannes,Ming Jin,Zhiyu Li,Defen Shen,Chi-Chao Chan,Baoying Liu,Shayma Jawad,Yujuan Wang,Sima Hirani,Lai Wei,H Nida Sen

doi:10.1186/1479-5876-12-152

Abstract

BackgroundSarcoidosis is a chronic inflammatory disease with a systemic granulomatous disorder affecting multiple organs including the eye. Both CD4+ T cell and macrophage have been linked to the pathogenesis of the disease.MethodsThe expression of IL-17RC was measured using FACS,immunohistochemistry and real-time PCR. Serum level of IL-17 was detected using ELISA.ResultsAn elevated expression of IL-17RC on CD8+ T cells in peripheral blood was found in patients with ocular sarcoidosis as compared to healthy controls. Interestingly, we found a significant increase in the serum level of IL-17 in patients with ocular sarcoidosis as compared to healthy controls, which may be responsible for the induction of IL-17RC on CD8+ cells. In addition, IL-17RC appeared only in the retinal tissue of the patient with clinically active sarcoidosis.ConclusionsOur results suggested a potential involvement of IL-17RC+CD8+ T cells in pathogenesis of ocular sarcoidosis.

Highlights

Sarcoidosis is a chronic inflammatory disease with a systemic granulomatous disorder affecting multiple organs including the eye
Consistent with the above results that an elevated expression of IL-17RC was found on CD8+ T cells in peripheral blood from patients with ocular sarcoidosis (Figure 2), more IL-17RC+ cells were found in the cultures of CD8+ T cells, stimulated by plate-bound anti-CD3 and anti-CD28 antibodies for 3 days, from sarcoidosis patients than in the culture of CD8+ T cells from healthy controls (Figure 3B)
We have reported that 10% of the lymphocytic infiltration was CD8+ T cells but these cells were rarely found within granulomas in an eye with clinically active sarcoidosis [31]

Summary

Methods

Patients All protocols were approved by institutional review boards, and written informed consents were provided by the patients to the National Institutes of Health. CD8+ T cells were isolated from peripheral blood of healthy controls or Sarcoidosis patients and stimulated by plate-bound anti-CD3 and antiCD28 antibodies with or without IL-17 for 3 days. Consistent with the above results that an elevated expression of IL-17RC was found on CD8+ T cells in peripheral blood from patients with ocular sarcoidosis (Figure 2), more IL-17RC+ cells were found in the cultures of CD8+ T cells, stimulated by plate-bound anti-CD3 and anti-CD28 antibodies for 3 days, from sarcoidosis patients than in the culture of CD8+ T cells from healthy controls (Figure 3B). IL17RC expression was below the detectable level in both the inflammatory and normal retina of the eye with clinically quiet disease (Figure 4E). In the eye with clinically active sarcoidosis, IL17RC RNA expression averaged at 108.1 fold higher in the retinal inflammatory lesion but only 14.2 fold

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Conclusions