Site-specific immunophenotyping of keloid disease demonstrates immune upregulation and the presence of lymphoid aggregates

British Journal of Dermatology

Volumn 167, Issue 5, 2012, Pages 1053-1066

  Bagabir, R ^a   Byers, R J ^b,c   Chaudhry, I H ^c   Muller W ^a   Paus, R ^a,d   Bayat, A ^a,e  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c MANCHESTER UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

^d UNIVERSITY OF LÜBECK   (Germany)

^e UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CD163 ANTIGEN; CD20 ANTIGEN; CD3 ANTIGEN; CD4 ANTIGEN; CD68 ANTIGEN; CD79A ANTIGEN; CD8 ANTIGEN; COMPLEMENT COMPONENT C3D RECEPTOR; KI 67 ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; OX40 LIGAND; SYNDECAN 1; VASCULAR CELL ADHESION MOLECULE 1;

ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; HISTOCHEMISTRY; HUMAN; HUMAN TISSUE; IMMUNOPHENOTYPING; IMMUNOREGULATION; INFLAMMATORY INFILTRATE; KELOID; KELOID ASSOCIATED LYMPHOID TISSUE; LANGERHANS CELL; LYMPHOID CELL; LYMPHOID TISSUE; MACROPHAGE; MAST CELL; MORPHOMETRICS; MUCOSA ASSOCIATED LYMPHOID TISSUE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SCAR; SKIN BIOPSY; T LYMPHOCYTE; UPREGULATION;

BIOLOGICAL MARKERS; BIOPSY; CASE-CONTROL STUDIES; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMMUNOPHENOTYPING; KELOID; LYMPHOID TISSUE; MAST CELLS; STATISTICS, NONPARAMETRIC; UP-REGULATION;

EID: 84868155868     PISSN: 00070963     EISSN: 13652133     Source Type: Journal    
DOI: 10.1111/j.1365-2133.2012.11190.x     Document Type: Article

References (69)

1. Shih B, Garside E, McGrouther DA, Bayat A,. Molecular dissection of abnormal wound healing processes resulting in keloid disease. Wound Repair Regen 2009; 18: 139-53.
2. Syed F, Ahmadi E, Iqbal SA, et al. Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy. Br J Dermatol 2010; 164: 83-96.
3. Juckett G, Hartman-Adams H,. Management of keloids and hypertrophic scars. Am Fam Physician 2009; 80: 253-60.
4. Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002; 110: 560-71.
5. Santucci M, Borgognoni L, Reali U, et al. Keloids and hypertrophic scars of Caucasians show distinctive morphologic and immunophenotypic profiles. Virchows Arch 2001; 438: 457-63.
6. Gabrielli A, Avvedimento EV, Krieg T,. Scleroderma. N Engl J Med 2009; 360: 1989-2003.
7. Koonin AJ,. The aetiology of keloids: a review of the literature and a new hypothesis. S Afr Med J 1964; 38: 913-16.
8. Sidgwick GP, Bayat A,. Extracellular matrix molecules implicated in hypertrophic and keloid scarring. J Eur Acad Dermatol Venereol 2012; 26: 141-52.
9. Lucas T, Waisman A, Ranjan R, et al. Differential roles of macrophages in diverse phases of skin repair. J Immunol 2010; 184: 3964-77.
10. Castagnoli C, Stella M, Magliacani G,. Role of T-lymphocytes and cytokines in post-burn hypertrophic scars. Wound Repair Regen 2002; 10: 107-8.
11. Bernabei P, Rigamonti L, Ariotti S, et al. Functional analysis of T lymphocytes infiltrating the dermis and epidermis of post-burn hypertrophic scar tissues. Burns 1999; 25: 43-8.
12. Wang J, Jiao H, Stewart TL, et al. Increased TGF-β-producing CD4+ T lymphocytes in postburn patients and their potential interaction with dermal fibroblasts in hypertrophic scarring. Wound Repair Regen 2007; 15: 530-9.
13. Tredget EE, Yang L, Delehanty M, et al. Polarized Th2 cytokine production in patients with hypertrophic scar following thermal injury. J Interferon Cytokine Res 2006; 26: 179-89.
14. Chizzolini C, Brembilla NC, Montanari E, et al. Fibrosis and immune dysregulation in systemic sclerosis. Autoimmun Rev 2011; 10: 276-81.
15. Wong VW, Paterno J, Sorkin M, et al. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation. FASEB J 2011; 25: 4498-510.
16. Martin CW, Muir IF,. The role of lymphocytes in wound healing. Br J Plast Surg 1990; 43: 655-62.
17. Boyce DE, Ciampolini J, Ruge F, et al. Inflammatory cell subpopulations in keloid scars. Br J Plast Surg 2001; 54: 511-16.
18. Shaker SA, Ayuob NN, Hajrah NH,. Cell talk: a phenomenon observed in the keloid scar by immunohistochemical study. Appl Immunohistochem Mol Morphol 2011; 19: 153-9.
19. Zhang Q, Yamaza T, Kelly AP, et al. Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. PLoS One 2009; 4: e7798.
20. Bagabir RA, Syed F, Rautemaa R, et al. Upregulation of toll-like receptors (TLRs) 6, 7, and 8 in keloid scars. J Invest Dermatol 2011; 131: 2128-30.
21. Tan KT, Shah N, Pritchard SA, et al. The influence of surgical excision margins on keloid prognosis. Ann Plast Surg 2010; 64: 55-8.
22. Christoph T, Müller-Röver S, Audring H, et al. The human hair follicle immune system: cellular composition and immune privilege. Br J Dermatol 2000; 142: 862-73.
23. Ito N, Sugawara K, Bodo E, et al. Corticotropin-releasing hormone stimulates the in situ generation of mast cells from precursors in the human hair follicle mesenchyme. J Invest Dermatol 2010; 130: 995-1004.
24. Barrow E, Evans DG, McMahon R, et al. A comparative study of quantitative immunohistochemistry and quantum dot immunohistochemistry for mutation carrier identification in Lynch syndrome. J Clin Pathol 2011; 64: 208-14.
25. Byers RJ, Hitchman ER,. Quantum dots brighten biological imaging. Prog Histochem Cytochem 2010; 45: 201-37.
26. Wrõbel T, Dziegiel P, Mazur G, et al. LYVE-1 expression on high endothelial venules (HEVs) of lymph nodes. Lymphology 2005; 38: 107-10.
27. Banerji S, Ni J, Wang SX, et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 1999; 144: 789-801.
28. Rangel-Moreno J, Hartson L, Navarro C, et al. Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J Clin Invest 2006; 116: 3183-94.
29. Kotani A, Hori T, Fujita T, et al. Involvement of OX40 ligand+ mast cells in chronic GVHD after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 39: 373-5.
30. Lau SK, Chu PG, Weiss LM,. CD163. Am J Clin Pathol 2004; 122: 794-801.
31. Komohara Y, Hirahara J, Horikawa T, et al. AM-3K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype. J Histochem Cytochem 2006; 54: 763-71.
32. Ito T, Ito N, Saathoff M, et al. Immunology of the human nail apparatus: the nail matrix is a site of relative immune privilege. J Invest Dermatol 2005; 125: 1139-48.
33. Xia W, Phan TT, Lim IJ, et al. Complex epithelial-mesenchymal interactions modulate transforming growth factor-β expression in keloid-derived cells. Wound Repair Regen 2004; 12: 546-56.
34. Lim IJ, Phan TT, Bay BH, et al. Fibroblasts cocultured with keloid keratinocytes: normal fibroblasts secrete collagen in a keloidlike manner. Am J Physiol Cell Physiol 2002; 283: C212-22.
35. Song E, Ouyang N, Hörbelt M, et al. Influence of alternatively and classically activated macrophages on fibrogenic activities of human fibroblasts. Cell Immunol 2000; 204: 19-28.
36. Wynn TA, Barron L,. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 2010; 30: 245-57.
37. Lolmede K, Campana L, Vezzoli M, et al. Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways. J Leukoc Biol 2009; 85: 779-87.
38. Movahedi K, Laoui D, Gysemans C, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res 2010; 70: 5728-39.
39. Boyle JJ, Harrington HA, Piper E, et al. Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype. Am J Pathol 2009; 174: 1097-108.
40. Drayton DL, Liao S, Mounzer RH, et al. Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 2006; 7: 344-53.
41. Cupedo T, Jansen W, Kraal G, et al. Induction of secondary and tertiary lymphoid structures in the skin. Immunity 2004; 21: 655-67.
42. Mueller SN, Germain RN,. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat Rev Immunol 2009; 9: 618-29.
43. Lim IJ, Phan TT, Song C, et al. Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. Plast Reconstr Surg 2001; 107: 797-808.
44. Castagnoli C, Trombotto C, Ondei S, et al. Characterization of T-cell subsets infiltrating post-burn hypertrophic scar tissues. Burns 1997; 23: 565-72.
45. Sawada Y, Mori T, Yamada S, et al. Keloid exacerbation associated with adult T-cell leukemia/lymphoma cell infiltration. Eur J Dermatol 2011; 21: 646-7.
46. Cai Y, Shen X, Ding C, et al. Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation. Immunity 2011; 35: 596-610.
47. Yen D, Cheung J, Scheerens H, et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 2006; 116: 1310-16.
48. Akaishi S, Ogawa R, Hyakusoku H,. Keloid and hypertrophic scar: neurogenic inflammation hypotheses. Med Hypotheses 2008; 71: 32-8.
49. Arck PC, Slominski A, Theoharides TC, et al. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol 2006; 126: 1697-704.
50. Zhang Q, Oh CK, Messadi DV, et al. Hypoxia-induced HIF-1 [alpha] accumulation is augmented in a co-culture of keloid fibroblasts and human mast cells: involvement of ERK1/2 and PI-3K/Akt. Exp Cell Res 2006; 312: 145-55.
51. Moyer KE, Saggers GC, Ehrlich HP,. Mast cells promote fibroblast populated collagen lattice contraction through gap junction intercellular communication. Wound Repair Regen 2004; 12: 269-75.
52. Pistorio AL, Ehrlich HP,. Modulatory effects of connexin-43 expression on gap junction intercellular communications with mast cells and fibroblasts. J Cell Biochem 2011; 112: 1441-9.
53. Abe M, Kurosawa M, Ishikawa O, et al. Effect of mast cell-derived mediators and mast cell-related neutral proteases on human dermal fibroblast proliferation and type I collagen production. J Allergy Clin Immunol 2000; 106: 78-84.
54. Gruber BL, Kew RR, Jelaska A, et al. Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 1997; 158: 2310-17.
55. Ong CT, Khoo YT, Mukhopadhyay A, et al. Comparative proteomic analysis between normal skin and keloid scar. Br J Dermatol 2010; 162: 1302-15.
56. Nakae S, Suto H, Iikura M, et al. Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol 2006; 176: 2238-48.
57. Kashiwakura J, Yokoi H, Saito H, Okayama Y,. T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. J Immunol 2004; 173: 5247-57.
58. Rodero MP, Khosrotehrani K,. Skin wound healing modulation by macrophages. Int J Clin Exp Pathol 2010; 3: 643-53.
59. Xie Y, Zhang X, Wakasugi S, et al. Immunohistochemical characterization of the cellular infiltrate in localized scleroderma. Int J Dermatol 2008; 47: 438-42.
60. Murray PJ, Wynn TA,. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011; 11: 723-37.
61. Bagabir R, Syed F, Paus R, et al. Long-term organ culture of keloid disease tissue. Exp Dermatol 2012; 21: 376-81.
62. Peduto L, Dulauroy S, Lochner M, et al. Inflammation recapitulates the ontogeny of lymphoid stromal cells. J Immunol 2009; 182: 5789-99.
63. Lochner M, Ohnmacht C, Presley L, et al. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells. J Exp Med 2011; 208: 125-34.
64. Sura R, Colombel JF, van Kruiningen HJ,. Lymphatics, tertiary lymphoid organs and the granulomas of Crohn's disease: an immunohistochemical study. Aliment Pharmacol Ther 2011; 33: 930-9.
65. Marchal-Somme J, Uzunhan Y, Marchand-Adam S, et al. Cutting edge: nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol 2006; 176: 5735-9.
66. Mebius RE,. Organogenesis of lymphoid tissues. Nat Rev Immunol 2003; 3: 292-303.
67. Cesta MF,. Normal structure, function, and histology of mucosa-associated lymphoid tissue. Toxicol Pathol 2006; 34: 599-608.
68. Wang X-Q, Phillips GE, Wilkie I, et al. Microscopic inflammatory foci in burn scars: data from a porcine burn model. J Cutan Pathol 2010; 37: 530-4.
69. Yeh SW, Lee WR, Hu CH, et al. Kimura's disease mimicking an earlobe keloid. Clin Exp Dermatol 2009; 35: e97-9.