CCL3, IL‐7, IL‐13 and IFNγ transcripts are increased in skin's biopsy of systemic sclerosis

Abstract

Although several cytokines and chemokines have been investigated as possible mediators of fibrosis in systemic sclerosis (SSc), specific correlation between cytokines and organ involvement have not been found yet, and a cytokine profile characteristic of SSc is far to be identified. We studied the profile of antifibrotic and profibrotic transcripts involved in skin of SSc patients. The mRNA expression was detected by fluorescence‐based quantitative real‐time PCR (qPCR) in skin's biopsies from 14 patients with SSc and 5 healthy controls. PDGF‐A, CTGF, CCL3, IL‐6, IL‐13, IL‐7, IFNγ, IL‐17, IL‐22 and RORc were analysed in these samples. CCL3, IL‐7, IL‐13 and IFN‐γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls. We also found a positive correlation between CCL3 and IL‐7 transcripts (P = 0.0050 r = 0.7187). Furthermore, we observed that patients with lung involvement had lower expression of PDGF‐A (P = 0.0385). We found an increase in IL‐7, IFN‐γ, CCL3 and IL‐13 relative mRNA expressions on the skin's biopsy of patients with SSc, and a positive correlation between IL‐7 and CCL3. These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies.

Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development

“…IL-13 (upregulated by HCMV > 21 fold) has been shown to play a role in many inflammatory and fibrotic diseases, including SSc, and appears to be necessary in the effector phase of inflammation and fibrosis [ 72 , 73 ]. In particular, IL-13 is significantly expressed in skin biopsies of SSc patients and its levels were found markedly increased in parallel with the progression of cutaneous fibrosis in bleomycin-induced SSc murine model [ 74 , 75 ]. CCL2, CCL11, and SERPINA1 transcripts were also upregulated by HCMV (up to 39, 43, and 22 fold, respectively).…”

“…CCL3 (upregulated by HCMV > 48 fold) has been demonstrated to play a role in dermal and pulmonary fibrosis in a murine sclerodermatous disease model [ 81 ] and, recently, CCL3 transcripts were found increased in skin biopsies of SSc patients [ 74 ].…”

“…By summarizing the results obtained in this in vitro study on the modulation of several pro-fibrotic factors induced by HCMV and/or HHV-6A, it is worthy to note that although a number of them are often altered in different autoimmune diseases [ 89 ], most of them have been described to be up- or downregulated in SSc, as already highlighted above [ 15 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ].…”

More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Authors report that intradermal RS‐504393 significantly lowers indicators of skin fibrosis, including myofibroblast numbers, collagen synthesis and TGFβ1 levels. Another study by Henderson et al 55 report that levels of DKK1, a negative regulator of WNT signalling, become reduced in skin biopsies as well as in fibroblasts from patients with systemic sclerosis, a chronic autoimmune disorder manifested by activation of contractile myofibroblasts and excessive ECM deposition 56–58 . Authors also report that DKK1 expression in systemic sclerosis fibroblasts is under the control of miR33a‐3p.…”

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

“…The imbalance and dysfunction of Th17/Treg cells are crucial to the generation of SSc (168). Quantitative analysis of Th17 cytokines in lesional skin of SSc showed that the expression of IL-17A, IL-13, IL-22, and IL-26 mRNA are higher compared with healthy control (169,170). The levels of circulating Th17 cells and IL-17 elevated in serum of patients with SSc.…”