49, 2705 boulevard Laurier, Quebec, QC, G1V 4G2, Canada. 2Walter and Eliza Hall Institute of Medical Investigation, 1G Royal Parade, Parkville, VIC 3050, Australia.Received: 6 October 2012 Revised: 18 March 2013 Accepted: 9 July 2013 Published: 9 July 2013 References 1. Martinon F: Mechanisms of uric acid crystal-mediated autoinflammation. Immunol Rev 2010, 233:218-232. two. Weaver AL: Epidemiology of gout. Cleve Clin J Med 2008, 75(Suppl 5): S9-S12. 3. Busso N, So A: Mechanisms of inflammation in gout. Arthritis Res Ther 2010, 12:206. four. Popa-Nita O, Naccache PH: Crystal-induced neutrophil activation. Immunol Cell Biol 2010, 88:32-40. 5. Da on M, Jaeger S, Du Pasquier L, Vivier E: Immunoreceptor tyrosinebased inhibition motifs: a quest inside the previous and future. Immunol Rev 2008, 224:11-43. 6. Pyz E, Marshall AS, Gordon S, Brown GD: C-type lectin-like receptors on myeloid cells. Ann Med 2006, 38:242-251. 7. Steevels TA, Meyaard L: Immune inhibitory receptors: important regulators of phagocyte function. Eur J Immunol 2011, 41:575-587. 8. Marshall AS, Willment JA, Lin HH, Williams DL, Gordon S, Brown GD: Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that’s predominantly expressed on granulocytes and monocytes. J Biol Chem 2004, 279:14792-14802. 9. Marshall AS, Willment JA, Pyz E, Dennehy KM, Reid DM, Dri P, Gordon S, Wong SY, Brown GD: Human MICL (CLEC12A) is differentially glycosylated and is down-regulated following cellular activation. Eur J Immunol 2006, 36:2159-2169. ten. Chen CH, Floyd H, Olson NE, Magaletti D, Li C, Draves K, Clark EA: Dendritic-cell-associated C-type lectin two (DCAL-2) alters dendritic-cell maturation and cytokine production. Blood 2006, 107:1459-1467. 11. Han Y, Zhang M, Li N, Chen T, Zhang Y, Wan T, Cao X: KLRL1, a novel killer cell lectinlike receptor, inhibits organic killer cell cytotoxicity. Blood 2004, 104:2858-2866. 12. Bakker AB, van den Oudenrijn S, Bakker AQ, Feller N, van Meijer M, Bia JA, Jongeneelen MA, Visser TJ, Bijl N, Geuijen CA, Marissen WE, Radosevic K, Throsby M, Schuurhuis GJ, Ossenkoppele GJ, de Kruif J, Goudsmit J, Kruisbeek AM: C-type lectin-like molecule-1: a novel myeloid cell surface marker connected with acute myeloid leukemia. Cancer Res 2004, 64:8443-8450. 13. Lahoud MH, Proietto AI, Ahmet F, Kitsoulis S, Eidsmo L, Wu L, Sathe P, Pietersz S, Chang HW, Walker ID, Maraskovsky E, Braley H, Lew AM, Wright MD, Heath WR, Shortman K, Caminschi I: The C-type lectin Clec12A present on mouse and human dendritic cells can serve as a target for antigen delivery and enhancement of antibody responses.Price of 20045-77-6 J Immunol 2009, 182:7587-7594.1073354-99-0 Price 14.PMID:23558135 Naccache PH, Grimard M, Roberge CJ, Gilbert C, Lussier A, de M icis R, Poubelle PE: Crystal-induced neutrophil activation. I. Initiation andConclusion Our findings strongly suggest that MICL might play a pathogenic role in gout by being among the targets of MSU. We propose that MSU downregulate the inhibitory activity of MICL by diminishing its expression, resulting within the full activation of human neutrophils. In contrast, colchicine has the opposite effect on the cell surface expression of MICL. MICL is thus a possible therapeutic target for gout. Additional characterization of your function of MICL in MSU-induced neutrophil activation plus the molecular events driving MICL function is necessary to shed light around the pathogenic part of MICL in gout and its possible as a drug target. Since neutrophils are the principal play.