Overexpression of IL-17RC associated with ocular sarcoidosis

Journal of Translational Medicine

Lai Wei³  Robert B Nussenblatt²  Chi-Chao Chan²  H Nida Sen²  Shayma Jawad²  Sima Hirani²  Zhiyu Li²  Susan Hannes²  Ping Chen²  Defen Shen²  Baoying Liu²  Yujuan Wang³  Ming Jin¹  Wenting Wu¹ 

[1] Department of Ophthalmology, China-Japan Friendship Hospital, Beijing, China;Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA;State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

关键词: CD8;    IL-17RC;    Ocular sarcoidosis;   

Others  :  810812
DOI  :  10.1186/1479-5876-12-152

 received in 2014-03-08, accepted in 2014-05-14,  发布年份 2014

【 摘 要 】

Background

Sarcoidosis 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.

Methods

The expression of IL-17RC was measured using FACS,immunohistochemistry and real-time PCR. Serum level of IL-17 was detected using ELISA.

Results

An 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.

Conclusions

Our results suggested a potential involvement of IL-17RC⁺CD8⁺ T cells in pathogenesis of ocular sarcoidosis.

【 授权许可】

   
2014 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Jamilloux Y, Kodjikian L, Broussolle C, Seve P: Sarcoidosis and uveitis. Autoimmun Rev 2014. doi:10.1016/j.autrev.2014.04.001
• [2]Kawagoe T, Mizuki N: Sarcoidosis. Curr Opin Ophthalmol 2011, 22:502-507.
• [3]Culver DA, Newman LS, Kavuru MS: Gene-environment interactions in sarcoidosis: challenge and opportunity. Clin Dermatol 2007, 25:267-275.
• [4]Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC: Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997, 145:234-241.
• [5]Sverrild A, Backer V, Kyvik KO, Kaprio J, Milman N, Svendsen CB, Thomsen SF: Heredity in sarcoidosis: a registry-based twin study. Thorax 2008, 63:894-896.
• [6]Hofmann S, Franke A, Fischer A, Jacobs G, Nothnagel M, Gaede KI, Schurmann M, Muller-Quernheim J, Krawczak M, Rosenstiel P, Schreiber S: Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nat Genet 2008, 40:1103-1106.
• [7]Hofmann S, Fischer A, Till A, Muller-Quernheim J, Hasler R, Franke A, Gade KI, Schaarschmidt H, Rosenstiel P, Nebel A, Schurmann M, Nothnagel M, Schreiber S: A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1. Eur Respir J 2011, 38:1127-1135.
• [8]Adrianto I, Lin CP, Hale JJ, Levin AM, Datta I, Parker R, Adler A, Kelly JA, Kaufman KM, Lessard CJ, Moser KL, Kimberly RP, Harley JB, Iannuzzi MC, Rybicki BA, Montgomery CG: Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. PLoS One 2012, 7:e43907.
• [9]Valentonyte R, Hampe J, Huse K, Rosenstiel P, Albrecht M, Stenzel A, Nagy M, Gaede KI, Franke A, Haesler R, Koch A, Lengauer T, Seegert D, Reiling N, Ehlers S, Schwinger E, Platzer M, Krawczak M, Muller-Quernheim J, Schurmann M, Schreiber S: Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet 2005, 37:357-364.
• [10]Rybicki BA, Walewski JL, Maliarik MJ, Kian H, Iannuzzi MC: The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. Am J Hum Genet 2005, 77:491-499.
• [11]Sato H, Woodhead FA, Ahmad T, Grutters JC, Spagnolo P, van den Bosch JM, Maier LA, Newman LS, Nagai S, Izumi T, Wells AU, du Bois RM, Welsh KI: Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups. Hum Mol Genet 2010, 19:4100-4111.
• [12]Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI: CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis. Eur Respir J 2010, 35:324-330.
• [13]Grunewald J: Review: role of genetics in susceptibility and outcome of sarcoidosis. Semin Respir Crit Care Med 2010, 31:380-389.
• [14]Thompson IA, Liu B, Sen HN, Jiao X, Katamay R, Li Z, Hu M, Hejtmancik F, Nussenblatt RB: Association of complement factor H tyrosine 402 histidine genotype with posterior involvement in sarcoid-related uveitis. Am J Ophthalmol 2013, 155:1068-1074.e1061.
• [15]Newman LS, Rose CS, Bresnitz EA, Rossman MD, Barnard J, Frederick M, Terrin ML, Weinberger SE, Moller DR, McLennan G, Hunninghake G, DePalo L, Baughman RP, Iannuzzi MC, Judson MA, Knatterud GL, Thompson BW, Teirstein AS, Yeager H Jr, Johns CJ, Rabin DL, Rybicki BA, Cherniack R: A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med 2004, 170:1324-1330.
• [16]Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, Takizawa T, Koike M, Kudoh S, Costabel U, Guzman J, Rizzato G, Gambacorta M, du Bois R, Nicholson AG, Sharma OP, Ando M: Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol 2002, 40:198-204.
• [17]Robinson LA, Smith P, Sengupta DJ, Prentice JL, Sandin RL: Molecular analysis of sarcoidosis lymph nodes for microorganisms: a case–control study with clinical correlates. BMJ Open 2013, 3:e004065.
• [18]Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S: Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol 2011, 45:899-905.
• [19]Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M, van den Blink B: Granuloma formation in pulmonary sarcoidosis. Front Immunol 2013, 4:437.
• [20]Heron M, Claessen AM, Grutters JC, van den Bosch JM: T-cell activation profiles in different granulomatous interstitial lung diseases–a role for CD8 + CD28(null) cells? Clin Exp Immunol 2010, 160:256-265.
• [21]Tondell A, Ro AD, Asberg A, Borset M, Moen T, Sue-Chu M: Activated CD8 T cells and NKT cells in BAL fluid improve diagnostic accuracy in sarcoidosis. Lung 2013, 192(1):133-40.
• [22]Grunewald J, Eklund A: Role of CD4+ T cells in sarcoidosis. Proc Am Thorac Soc 2007, 4:461-464.
• [23]Dagur PK, Biancotto A, Wei L, Sen HN, Yao M, Strober W, Nussenblatt RB, McCoy JP Jr: MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17A and are significantly elevated in inflammatory autoimmune diseases. J Autoimmun 2011, 37:319-327.
• [24]Ten Berge B, Paats MS, Bergen IM, van den Blink B, Hoogsteden HC, Lambrecht BN, Hendriks RW, Kleinjan A: Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis. Rheumatology (Oxford) 2012, 51:37-46.
• [25]Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE: TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 2007, 13:711-718.
• [26]Curtis MM, Way SS: Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens. Immunology 2009, 126:177-185.
• [27]Korn T, Bettelli E, Oukka M, Kuchroo VK: IL-17 and Th17 Cells. Annu Rev Immunol 2009, 27:485-517.
• [28]Wei L, Liu B, Tuo J, Shen D, Chen P, Li Z, Liu X, Ni J, Dagur P, Sen HN, Jawad S, Ling D, Park S, Chakrabarty S, Meyerle C, Agron E, Ferris FL 3rd, Chew EY, McCoy JP, Blum E, Francis PJ, Klein ML, Guymer RH, Baird PN, Chan CC, Nussenblatt RB: Hypomethylation of the IL17RC promoter associates with age-related macular degeneration. Cell Rep 2012, 2:1151-1158.
• [29]Hu Y, Ota N, Peng I, Refino CJ, Danilenko DM, Caplazi P, Ouyang W: IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 2010, 184:4307-4316.
• [30]Urbankowski T, Hoser G, Domagala-Kulawik J: Th1/Th2/Th17related cytokines in the bronchoalveolar lavage fluid of patients with sarcoidosis: association with smoking. Pol Arch Med Wewn 2012, 122:320-325.
• [31]Chan CC, Wetzig RP, Palestine AG, Kuwabara T, Nusenblatt RB: Immunohistopathology of ocular sarcoidosis. Report of a case and discussion of immunopathogenesis. Arch Ophthalmol 1987, 105:1398-1402.
• [32]Candia J, Maunu R, Driscoll M, Biancotto A, Dagur P, McCoy JP Jr, Sen HN, Wei L, Maritan A, Cao K, Nussenblatt RB, Banavar JR, Losert W: From cellular characteristics to disease diagnosis: uncovering phenotypes with supercells. PLoS Comput Biol 2013, 9:e1003215.
• [33]Zhou T, Zhang W, Sweiss NJ, Chen ES, Moller DR, Knox KS, Ma SF, Wade MS, Noth I, Machado RF, Garcia JG: Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis. PLoS One 2012, 7:e44818.