Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

• Main Authors: Klein Michael L, Chan Chi-Chao, Agron Elvira, Chakrabarty Sagarika, Li Zhiyu, Sen H Nida, Tuo Jingsheng, Meyerle Catherine, Wei Lai, Liu Baoying, Chew Emily, Ferris Frederick, Nussenblatt Robert B
• Format: Article
• Language: English
• Published: BMC 2011-07-01
• Series: Journal of Translational Medicine
• Online Access: http://www.translational-medicine.com/content/9/1/111

<p>Abstract</p> <p>Background</p> <p>Age related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH), the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a) have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD.</p> <p>Methods</p> <p>Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500.</p> <p>Results</p> <p>We show that C5a promotes interleukin (IL)-22 and IL-17 expression by human CD4⁺T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4⁺cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls.</p> <p>Conclusions</p> <p>Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.</p>