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24.05.2016 | Original Paper

Immunohistochemical study of toll-like receptors 2, 4, and 9 expressions in pemphigus and bullous pemphigoid lesions

verfasst von: Xiu-Kun Sun, Jun-Fan Chen, Hong Shen

Erschienen in: Archives of Dermatological Research | Ausgabe 6/2016

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Abstract

Pemphigus and bullous pemphigoid (BP) are severe autoimmune skin diseases. Whether innate immunity could be a trigger or a part of the pathogeneses is unknown. Toll-like receptors (TLRs) are important components of the innate immune system, with no previous evaluation of TLRs in autoimmune bullous diseases. This work aims to investigate TLRs 2, 4, and 9 expressions in pemphigus and bullous pemphigoid. Thirty-six patients with pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and six healthy controls were studied. Skin biopsies from the patients and the controls were examined immunohistochemically for TLR2, 4, and 9 expressions. The TLR4 expressed mainly at the basal layer of epidermis in controls, but in the cases with autoimmune bullous diseases, TLR4 staining located at basal layer and suprabasal layer, even superficial layer of epidermis. The immunostaining-intensity-distribution (IID) index of TLR4 in patients with PF (13.83, P = 0.001), PV (13.08, P = 0.003), and BP (11.42, P = 0.042) were significantly higher than that of the controls (6.17). TLR2 and TLR9 showed no significantly changes at epidermal expression (P > 0.05) compared with controls. There was no correlation found between the expressions of these TLRs. This work, thus, shows a re-localization of TLR4 expression sites with increased expression in pemphigus and bullous pemphigoid lesions. Targeting TLR4 signaling is expected to be a novel treatment strategy for autoimmune bullous diseases.

Ahmed A, Redmond HP, Wang JH (2013) Links between Toll-like receptor 4 and breast cancer. Oncoimmunology 2:e22945CrossRefPubMedPubMedCentral

Amagai M, Stanley JR (2012) Desmoglein as a target in skin disease and beyond. J Invest Dermatol 132(3 Pt 2):776–784CrossRefPubMed

Arakawa M, Dainichi T, Ishii N et al (2011) Lesional Th17 cells and regulatory T cells in bullous pemphigoid. Exp Dermatol 20:1022–1024CrossRefPubMed

Baker BS, Ovigne JM, Powles AV, Corcoran S, Fry L (2003) Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis. Br J Dermatol 148:670–679CrossRefPubMed

Bednar KJ, Ridgway WM (2014) Targeting innate immunity for treatment of type 1 diabetes. Immunotherapy 6:1239–1242CrossRefPubMed

Begon E, Michel L, Flageul B et al (2007) Expression, subcellular localization and cytokinic modulation of Toll-like receptors (TLRs) in normal human keratinocytes: TLR2 up-regulation in psoriatic skin. Eur J Dermatol 17:497–506PubMed

Bhattacharyya S, Varga J (2015) Emerging roles of innate immune signaling and toll-like receptors in fibrosis and systemic sclerosis. Curr Rheumatol Rep 17:474CrossRefPubMed

Brandt EB, Gibson AM, Bass S, Rydyznski C, Khurana Hershey GK (2013) Exacerbation of allergen-induced eczema in TLR4- and TRIF-deficient mice. J Immunol 191:3519–3525CrossRefPubMedPubMedCentral

Chaiyarit P, Kafrawy AH, Miles DA, Zunt SL, Van dis ML, Gregory RL (1999) Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins(CKs) and a unifying hypothesis of pathogenesis. J Oral Pathol Med 28:210–215CrossRefPubMed

10.

Chen L, Guo S, Ranzer MJ, DiPietro LA (2013) Toll-like receptor 4 has an essential role in early skin wound healing. J Invest Dermatol 133:258–267CrossRefPubMed

11.

Cheng TL, Lai CH, Chen PK et al (2015) Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression. J Invest Dermatol 135:1668–1675CrossRefPubMed

12.

Curry JL, Qin JZ, Bonish B et al (2003) Innate immune-related receptors in normal and psoriatic skin. Arch Pathol Lab Med 127:178–186PubMed

13.

Fan Y, Liu B (2015) Expression of Toll-like receptors in the mucosa of patients with ulcerative colitis. Exp Ther Med 9:1455–1459PubMedPubMedCentral

14.

Giudice GJ, Emery DJ, Zelickson BD, Anhalt GJ, Liu Z, Diaz LA (1993) Bullous pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous site on the BP180 ectodomain. J Immunol 151:5742–5750PubMed

15.

Harberts E, Zhou H, Fishelevich R, Liu J, Gaspari AA (2015) Ultraviolet radiation signaling through TLR4/MyD88 constrains DNA repair and plays a role in cutaneous immunosuppression. J Immunol 194:3127–3135CrossRefPubMed

16.

Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol 7:131–137CrossRefPubMed

17.

Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384CrossRefPubMed

18.

Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE 7:e47713CrossRefPubMedPubMedCentral

19.

Lebre MC, van der Aar AM, van Baarsen L et al (2006) Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol 127:331–341CrossRefPubMed

20.

Liu Y, Yin H, Zhao M, Lu Q (2014) TLR2 and TLR4 in autoimmune diseases: a comprehensive review. Clin Rev Allergy Immunol 47:136–147CrossRefPubMed

21.

Liu Z, Sui W, Zhao M et al (2008) Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model. J Autoimmun 31:331–338CrossRefPubMedPubMedCentral

22.

Marshak-Rothstein A (2006) Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 6:823–835CrossRefPubMed

23.

Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115:407–417CrossRefPubMedPubMedCentral

24.

Mempel M, Voelcker V, Kollisch G et al (2003) Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent. J Invest Dermatol 121:1389–1396CrossRefPubMed

25.

Mills KH (2011) TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol 11:807–822PubMed

26.

Morizane S, Yamasaki K, Mühleisen B et al (2012) Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol 132:135–143CrossRefPubMed

27.

O’Neill LA, Golenbock D, Bowie AG (2013) The history of Toll-like receptors—redefining innate immunity. Nat Rev Immunol 13:453–460CrossRefPubMed

28.

Panzer R, Blobel C, Fölster-Holst R, Proksch E (2014) TLR2 and TLR4 expression in atopic dermatitis, contact dermatitis and psoriasis. Exp Dermatol 23:364–366CrossRefPubMed

29.

Pivarcsi A, Bodai L, Rethi B (2003) Expression and function of Toll-like receptors 2 and 4 in human keratinocytes. Int Immunol 15:721–730CrossRefPubMed

30.

Salem SA, Abu-Zeid RM, Nada OH (2013) Immunohistochemical study of Toll-like receptors 1 and 2 expression in cutaneous lichen planus lesions. Arch Dermatol Res 305:125–131CrossRefPubMed

31.

Sebaratnam DF, Martin LK, Rubin AI et al (2011) Reversible relapse of pemphigus foliaceus triggered by topical imiquimod suggests that Toll-like receptor 7 inhibitors may be useful treatments for pemphigus. Clin Exp Dermatol 36:91–93CrossRefPubMed

32.

Selway JL, Kurczab T, Kealey T, Langlands K (2013) Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. BMC Dermatol 13:10CrossRefPubMedPubMedCentral

33.

Seung NR, Park EJ, Kim CW et al (2007) Comparison of expression of heat-shock protein 60, Toll-like receptors 2 and 4, and T-cell receptor gammadelta in plaque and guttate psoriasis. J Cutan Pathol 34:903–911CrossRefPubMed

34.

Song PI, Park YM, Abraham T et al (2002) Human keratinocytes express functional CD14 and toll-like receptor 4. J Invest Dermatol 119:424–432CrossRefPubMed

35.

Suga H, Sugaya M, Fujita H et al (2014) TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression. J Dermatol Sci 73:117–124CrossRefPubMed

36.

Ujiie H, Shimizu H (2012) Evidence for pathogenicity of autoreactive T cells in autoimmune bullous diseases shown by animal disease models. Exp Dermatol 21:901–905CrossRefPubMed

37.

Wang J, Hori K, Ding J et al (2011) Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. J Cell Physiol 226:1265–1273CrossRefPubMed

38.

Wu H, Chen G, Wyburn KR et al (2007) TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 117:2847–2859CrossRefPubMedPubMedCentral

39.

Yamasaki K, Kanada K, Macleod DT et al (2011) TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol 131:688–697CrossRefPubMed

40.

Yu LX, Yan L, Yang W et al (2014) Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun 5:5256CrossRefPubMed

Titel: Immunohistochemical study of toll-like receptors 2, 4, and 9 expressions in pemphigus and bullous pemphigoid lesions
verfasst von: Xiu-Kun Sun
Jun-Fan Chen
Hong Shen
Publikationsdatum: 24.05.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Dermatological Research / Ausgabe 6/2016
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-016-1656-5

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Immunohistochemical study of toll-like receptors 2, 4, and 9 expressions in pemphigus and bullous pemphigoid lesions

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