Innate Immunity in Systemic Sclerosis

Current Rheumatology Reports

Volumn 19, Issue 1, 2017, Pages

  Dowson, Christopher ^a   Simpson, Nathan ^a   Duffy, Laura ^a   O’Reilly, Steven ^a  

^a NORTHUMBRIA UNIVERSITY   (United Kingdom)

Author keywords

Autoimmune disease; Scleroderma; SSc; Systemic sclerosis

Indexed keywords

INFLAMMASOME; TOLL LIKE RECEPTOR; COMPLEMENT;

CELL STRESS; COMPLEMENT SYSTEM; EPIGENETICS; FIBROSIS; HUMAN; IMMUNE DYSREGULATION; IMMUNOPATHOGENESIS; INFLAMMATION; INNATE IMMUNITY; LIGAND BINDING; MACROPHAGE FUNCTION; MAST CELL; MONOCYTE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC SCLEROSIS; IMMUNOLOGY; MACROPHAGE;

COMPLEMENT SYSTEM PROTEINS; HUMANS; IMMUNITY, INNATE; INFLAMMASOMES; MACROPHAGES; MAST CELLS; MONOCYTES; SCLERODERMA, SYSTEMIC; TOLL-LIKE RECEPTORS;

EID: 85010878256     PISSN: 15233774     EISSN: 15346307     Source Type: Journal    
DOI: 10.1007/s11926-017-0630-3     Document Type: Review

References (69)

1. Valentini G, Black C. Systemic sclerosis. Best Pract Res Clin Rheumatol. 2002;16(5):807–16.
2. Yasuoka H. Recent treatments of interstitial lung disease with systemic sclerosis. Clin Med Insights Circ Respir Pulm Med. 2015;9 Suppl 1:97–110. doi:10.4137/CCRPM.S23315.
3. Chaisson NF, Hassoun PM. Systemic sclerosis-associated pulmonary arterial hypertension. Chest. 2013;144(4):1346–56. doi:10.1378/chest.12-2396.
4. Patterson KA, Roberts-Thomson PJ, Lester S, Tan JA, Hakendorf P, Rischmueller M, et al. Interpretation of an extended autoantibody profile in a well-characterized Australian systemic sclerosis (Scleroderma) cohort using principal components analysis. Arthritis Rheumatol. 2015;67(12):3234–44. doi:10.1002/art.39316.
5. Chang WS, Schollum J, White DH, Solanki KK. A cross-sectional study of autoantibody profiles in the Waikato systemic sclerosis cohort. New Zealand Clin Rheumatol. 2015;34(11):1921–7. doi:10.1007/s10067-015-2981-3.
6. Ochoa E, Martin JE, Assasi S, Beretta L, Carreira P, Guillen A, et al. Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis. Clin Exp Rheumatol. 2015;33(4 Suppl 91):S31–5.
7. Mierau R, Moinzadeh P, Riemekasten G, Melchers I, Meurer M, Reichenberger F, et al. Frequency of disease-associated and other nuclear autoantibodies in patients of the German Network for Systemic Scleroderma: correlation with characteristic clinical features. Arthritis Res Ther. 2011;13(5):R172. doi:10.1186/ar3495.
8. Dowson C, O’Reilly S. DNA methylation in fibrosis. Eur J Cell Biol. 2016;95(9):323–30. doi:10.1016/j.ejcb.2016.06.003.
9. Martin SF. Adaptation in the innate immune system and heterologous innate immunity. Cell Mol Life Sci. 2014;71(21):4115–30. doi:10.1007/s00018-014-1676-2.
10. Yamamoto T. Autoimmune mechanisms of scleroderma and a role of oxidative stress. Self Nonself. 2011;2(1):4–10. doi:10.4161/self.2.1.14058.
11. Roelofs M, Joosten L, Abdollahi-Roodsaz S, Van Lieshout A, Sprong T, Van Den Hoogen F, et al. The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis Rheum. 2005;52(8):2313–22.
12. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, et al. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med. 2005;202(8):1131–9.
13. O’Reilly S, Cant R, Ciechomska M, Finnigan J, Oakley F, Hambleton S, et al. Serum amyloid A induces interleukin-6 in dermal fibroblasts via Toll-like receptor 2, interleukin-1 receptor-associated kinase 4 and nuclear factor-κB. Immunology. 2014;143(3):331–40.
14. Duffy L, O’Reilly SC. Toll-like receptors in the pathogenesis of autoimmune diseases: recent and emerging translational developments. ImmunoTargets Therapy. 2016;5:69.
15. Fullard N, O’Reilly S, editors. Role of innate immune system in systemic sclerosis. Seminars in immunopathology; 2015: Springer.
16. Lakota K, Carns M, Podlusky S, Mrak-Poljsak K, Hinchcliff M, Lee J, et al. Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis. PLoS One. 2015;10(1), e0110820.
17. O’Reilly S, Ciechomska M, Cant R, van Laar JM. Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-β (TGF-β) signaling promoting SMAD3 activation and fibrosis via Gremlin protein. J Biol Chem. 2014;289(14):9952–60.
18. Bhattacharyya S, Kelley K, Melichian DS, Tamaki Z, Fang F, Su Y, et al. Toll-like receptor 4 signaling augments transforming growth factor-β responses: a novel mechanism for maintaining and amplifying fibrosis in scleroderma. Am J Pathol. 2013;182(1):192–205.
19. Takahashi T, Asano Y, Ichimura Y, Toyama T, Taniguchi T, Noda S, et al. Amelioration of tissue fibrosis by toll-like receptor 4 knockout in murine models of systemic sclerosis. Arthritis Rheumatol. 2015;67(1):254–65.
20. Zhang Z, Lin C, Peng L, Ouyang Y, Cao Y, Wang J, et al. High mobility group box 1 activates Toll like receptor 4 signaling in hepatic stellate cells. Life Sci. 2012;91(5):207–12.
21. Stifano G, Affandi AJ, Mathes AL, Rice LM, Nakerakanti S, Nazari B, et al. Chronic Toll-like receptor 4 stimulation in skin induces inflammation, macrophage activation, transforming growth factor beta signature gene expression, and fibrosis. Arthritis Res Ther. 2014;16(4):1.
22. Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S, et al. FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling. Sci Transl Med. 2014;6(232):232ra50–ra50.
23. Ciechomska M, O’Reilly S, Suwara M, Bogunia-Kubik K, van Laar JM. MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-β activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS One. 2014;9(12), e115596.
24. Muro et al. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan Journal of Cell Biology 2003 162: 149–160.ᅟ
25. Booth AJ, Wood SC, Cornett AM, Dreffs AA, Lu G, Muro AF, et al. Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis. J Pathol. 2012;226(4):609–18.
26. •• Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X et al. Tenascin-C drives persistence of organ fibrosis. Nature communications. 2016;7. Shows the possible feed-forward loop with a fragment only expressed after tissue damage.
27. Brissett M, Veraldi KL, Pilewski JM, Medsger TA, Feghali-Bostwick CA. Localized expression of tenascin in systemic sclerosis–associated pulmonary fibrosis and its regulation by insulin-like growth factor binding protein 3. Arthritis Rheum. 2012;64(1):272–80.
28. Van Bon L, Cossu M, Loof A, Gohar F, Wittkowski H, Vonk M, et al. Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype. Ann Rheum Dis. 2014;73(8):1585–9.
29. Fang F, Marangoni RG, Zhou X, Yang Y, Ye B, Shangguang A, et al. TLR9 signaling is augmented in systemic sclerosis and elicits TGF-β-dependent fibroblast activation. Arthritis Rheumatol. 2016.
30. Kirillov V, Siler JT, Ramadass M, Ge L, Davis J, Grant G, et al. Sustained activation of toll-like receptor 9 induces an invasive phenotype in lung fibroblasts: possible implications in idiopathic pulmonary fibrosis. Am J Pathol. 2015;185(4):943–57.
31. Mutlu GM, Budinger GS, Wu M, Lam AP, Zirk A, Rivera S, et al. Proteasomal inhibition after injury prevents fibrosis by modulating TGF-β1 signalling. Thorax. 2012;67(2):139–46.
32. • Ciechomska M, O’Reilly S, Przyborski S, Oakley F, Bogunia-Kubik K, van Laar JM. Histone demethylation and toll-like receptor 8–dependent cross-talk in monocytes promotes transdifferentiation of fibroblasts in systemic sclerosis via Fra-2. Arthritis Rheumatol. 2016;68(6):1493–504. This is an important paper that describes the activation of monocytes by ssRNA and an alteration of lysine trimethylation on the histones that can aggravate fibrosis via upregulation of Fra2 and TIMP-1 expression.
33. Saigusa R, Asano Y, Taniguchi T, Yamashita T, Ichimura Y, Takahashi T, et al. Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis. Proc Natl Acad Sci. 2015;112(49):15136–41.
34. Farina GA, York MR, Di Marzio M, Collins CA, Meller S, Homey B, et al. Poly (I: C) drives type I IFN-and TGFβ-mediated inflammation and dermal fibrosis simulating altered gene expression in systemic sclerosis. J Investig Dermatol. 2010;130(11):2583–93.
35. Agarwal SK, Wu M, Livingston CK, Parks DH, Mayes MD, Arnett FC, et al. Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts. Arthritis Res Ther. 2011;13(1):1.
36. van Bon L, Cossu M, Scharstuhl A, Pennings BWC, Vonk MC, Vreman HJ, et al. Low heme oxygenase-1 levels in patients with systemic sclerosis are associated with an altered Toll-like receptor response: another role for CXCL4? Rheumatology. 2016;55(11):2066–73. doi:10.1093/rheumatology/kew251.
37. • Broen J, Bossini-Castillo L, Van Bon L, Vonk MC, Knaapen H, Beretta L, et al. A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators. Arthritis Rheum. 2012;64(1):264–71. This paper was the first to describe the rare SNP in TLR2 associated with a particular phenotype in SSc.
38. Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44(3):450–62. doi:10.1016/j.immuni.2016.02.015.
39. Fleischmajer R, Perlish JS, Reeves JR. Cellular infiltrates in scleroderma skin. Arthritis Rheum. 1977;20(4):975–84.
40. Higashi-Kuwata N, Jinnin M, Makino T, Fukushima S, Inoue Y, Muchemwa FC, et al. Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis. Arthritis Res Ther. 2010;12(4):R128. doi:10.1186/ar3066.
41. Lopez-Cacho JM, Gallardo S, Posada M, Aguerri M, Calzada D, Mayayo T, et al. Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease. Biomed Res Int. 2014;2014:148293. doi:10.1155/2014/148293.
42. Ghosh AK, Mori Y, Dowling E, Varga J. Trichostatin A blocks TGF-beta-induced collagen gene expression in skin fibroblasts: involvement of Sp1. Biochem Biophys Res Commun. 2007;354(2):420–6. doi:10.1016/j.bbrc.2006.12.204.
43. Higashi-Kuwata N, Makino T, Inoue Y, Takeya M, Ihn H. Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma. Exp Dermatol. 2009;18(8):727–9. doi:10.1111/j.1600-0625.2008.00828.x.
44. Raes G, Beschin A, Ghassabeh GH, De Baetselier P. Alternatively activated macrophages in protozoan infections. Curr Opin Immunol. 2007;19(4):454–9. doi:10.1016/j.coi.2007.05.007.
45. O’Reilly S. Epigenetics in fibrosis. Mol Asp Med. 2016.
46. Ciechomska M, van Laar J, O’Reilly S. Emerging role of epigenetics in systemic sclerosis pathogenesis. Genes Immun. 2014;15(7):433–9.
47. O’Reilly S, Ciechomska M, Fullard N, Przyborski S, van Laar JM. IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics. Sci Rep. 2016;6.
48. Distler O, Pap T, Kowal-Bielecka O, Meyringer R, Guiducci S, Landthaler M, et al. Overexpression of monocyte chemoattractant protein 1 in systemic sclerosis: role of platelet-derived growth factor and effects on monocyte chemotaxis and collagen synthesis. Arthritis Rheum. 2001;44(11):2665–78.
49. Harris CL, Heurich M, Rodriguez de Cordoba S, Morgan BP. The complotype: dictating risk for inflammation and infection. Trends Immunol. 2012;33(10):513–21. doi:10.1016/j.it.2012.06.001.
50. Triantafilou K, Hughes TR, Triantafilou M, Morgan BP. The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation. J Cell Sci. 2013;126(Pt 13):2903–13. doi:10.1242/jcs.124388.
51. Lachmann PJ, Hughes-Jones NC. Initiation of complement activation. Springer Semin Immunopathol. 1984;7(2–3):143–62.
52. Turner MW. The role of mannose-binding lectin in health and disease. Mol Immunol. 2003;40(7):423–9.
53. Harris CL, Pettigrew DM, Lea SM, Morgan BP. Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. J Immunol. 2007;178(1):352–9.
54. Senaldi G, Vergani D, McWhirter A, Black CM. Complement activation in progressive systemic sclerosis. Lancet. 1987;1(8542):1143–4.
55. Benbassat C, Schlesinger M, Luderschmidt C, Valentini G, Tirri G, Shoenfeld Y. The complement system and systemic sclerosis. Immunol Res. 1993;12(3):312–6.
56. Senaldi G, Lupoli S, Vergani D, Black CM. Activation of the complement system in systemic sclerosis. Relationship to clinical severity. Arthritis Rheum. 1989;32(10):1262–7.
57. Sprott H, Muller-Ladner U, Distler O, Gay RE, Barnum SR, Landthaler M, et al. Detection of activated complement complex C5b-9 and complement receptor C5a in skin biopsies of patients with systemic sclerosis (scleroderma). J Rheumatol. 2000;27(2):402–4.
58. Scambi C, La Verde V, De Franceschi L, Barausse G, Poli F, Benedetti F, et al. Comparative proteomic analysis of serum from patients with systemic sclerosis and sclerodermatous GVHD. Evidence of defective function of factor H. PLoS One. 2010;5(8), e12162. doi:10.1371/journal.pone.0012162.
59. Scambi C, Ugolini S, Jokiranta TS, De Franceschi L, Bortolami O, La Verde V, et al. The local complement activation on vascular bed of patients with systemic sclerosis: a hypothesis-generating study. PLoS One. 2015;10(2), e0114856. doi:10.1371/journal.pone.0114856.
60. Nichols EM, Barbour TD, Pappworth IY, Wong EK, Palmer JM, Sheerin NS, et al. An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy. Kidney Int. 2015;88(6):1314–22. doi:10.1038/ki.2015.233.
61. Osthoff M, Ngian GS, Dean MM, Nikpour M, Stevens W, Proudman S, et al. Potential role of the lectin pathway of complement in the pathogenesis and disease manifestations of systemic sclerosis: a case–control and cohort study. Arthritis Res Ther. 2014;16(6):480. doi:10.1186/s13075-014-0480-6.
62. Jordan JE, Montalto MC, Stahl GL. Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Circulation. 2001;104(12):1413–8.
63. Castellano G, Melchiorre R, Loverre A, Ditonno P, Montinaro V, Rossini M, et al. Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage. Am J Pathol. 2010;176(4):1648–59. doi:10.2353/ajpath.2010.090276.
64. Hugle T. Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly. 2014;144:w13999. doi:10.4414/smw.2014.13999.
65. Yukawa S, Yamaoka K, Sawamukai N, Shimajiri S, Kubo S, Miyagawa I, et al. Dermal mast cell density in fingers reflects severity of skin sclerosis in systemic sclerosis. Mod Rheumatol. 2013;23(6):1151–7. doi:10.1007/s10165-012-0813-8.
66. Artlett CM, Sassi-Gaha S, Rieger JL, Boesteanu AC, Feghali-Bostwick CA, Katsikis PD. The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis. Arthritis Rheum. 2011;63(11):3563–74.
67. Dieude P, Guedj M, Wipff J, Ruiz B, Riemekasten G, Airo P et al. NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis. Ann Rheum Dis. 2010:annrheumdis131243.
68. Bracey NA, Gershkovich B, Chun J, Vilaysane A, Meijndert HC, Wright JR, et al. Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome. J Biol Chem. 2014;289(28):19571–84.
69. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology. 2014;59(3):898–910.