Modulation of pulmonary fibrosis by IL-13Rα2

Lumsden, Robert V.; Worrell, Julie C.; Boylan, Denise; Walsh, S.; Cramton, Jennifer; Counihan, Ian; O’Beirne, Sarah L.; Medina, Maria Fe C.; Gauldie, Jack; Fabre, Aurélie; Donnelly, Seamas C.; Kane, Rosemary; Keane, Michael P.

doi:10.1152/ajplung.00120.2014

Cited by 36 publications

(22 citation statements)

References 34 publications

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“…Intriguingly, overexpression of IL-13 receptor alpha 2 (IL13RA2) protects against fibrosis [ 82 ]; instead, it was strongly downmodulated by HCMV, up to almost 800 fold.…”

Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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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

Arcangeletti

D’Accolti

Maccari

et al. 2020

IJMS

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Systemic sclerosis (SSc) is a severe autoimmune disorder characterized by vasculopathy and multi-organ fibrosis; its etiology and pathogenesis are still largely unknown. Herpesvirus infections, particularly by human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), have been suggested among triggers of the disease based on virological and immunological observations. However, the direct impact of HCMV and/or HHV-6 infection on cell fibrosis and apoptosis at the cell microenvironment level has not yet been clarified. Thus, this study aimed to investigate the effects of HCMV and HHV-6 infection on the induction of pro-fibrosis or pro-apoptosis conditions in primary human dermal fibroblasts, one of the relevant SSc target cells. The analysis, performed by microarray in in vitro HCMV- or HHV-6-infected vs. uninfected cells, using specific panels for the detection of the main cellular factors associated with fibrosis or apoptosis, showed that both viruses significantly modified the expression of at least 30 pro-fibrotic and 20 pro-apoptotic factors. Notably, several recognized pro-fibrotic factors were highly induced, and most of them were reported to be involved in vivo in the multifactorial and multistep pathogenic process of SSc, thus suggesting a potential role of both HCMV and HHV-6.

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“…Intriguingly, overexpression of IL-13 receptor alpha 2 (IL13RA2) protects against fibrosis [ 82 ]; instead, it was strongly downmodulated by HCMV, up to almost 800 fold.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Arcangeletti

D’Accolti

Maccari

et al. 2020

IJMS

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show abstract

“…52 In nonhematopoietic cells, IL-13 functions through a heterodimeric receptor composed of IL-4Ra and IL-13Ra1. 122,123 IL-13 also has a second receptor, IL-13Ra2. IL-13Ra2 binds IL-13 with high affinity and works as a decoy receptor.…”

Section: Il-13ra2 and Scratch Injurymentioning

confidence: 99%

Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis

Furue

Ulzii

Tanaka

et al. 2020

The Journal of Dermatology

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Mechanical scratching, a common external stress affecting the skin, is induced by various causes, such as pruritus. Scratch injury to epidermal keratinocytes upregulates the production and release of chemokine (C‐C motif) ligand 20 (CCL20) in vitro, which selectively chemoattracts interleukin (IL)‐17A‐producing immune cells that express chemokine (C‐C motif) receptor 6 (CCR6). In IL‐17A‐dominant psoriasis, scratch‐induced CCL20 upregulation and subsequent accumulation of IL‐17A‐producing immune cells and CCR6+ mature dendritic cells may trigger the development of psoriatic lesions, a process known as the Koebner phenomenon. In IL‐4/IL‐13‐dominant atopic dermatitis, pruritus and subsequent scratching are the primary symptoms. Scratch‐induced CCL20 production from keratinocytes may explain why IL‐17A levels are also elevated in atopic dermatitis. In contrast, mechanical scratching is likely to negatively regulate IL‐13 signaling by upregulating the expression of IL‐13 receptor α2, which serves as a decoy receptor for IL‐13 in keratinocytes. In this review, we summarize current reports on topics related to the pathogenic role of epidermal scratch injury in psoriasis and atopic dermatitis.

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“…For this reason, detailed mechanistic studies conducted with IL-4 and IL-13 inhibitors and IL-4 knock-out and IL13 knock-out mice have been happening to modulate pneumonitis and pulmonary [38][39][40][41]. Recently, there are reports that loss of IL-4 and IL-13 is trying to control the stimulation of AAMs, and ultimately it overcomes pneumonitis and fibrosis [42][43][44]. Conversely, Th1 subsets of CD4+ T lymphocytes, defined by their production of IFN-γ, have antifibrotic activity [45].…”

Section: Recruited Macrophages After Thoracic Irradiation Are Alternamentioning

confidence: 99%

Thoracic Irradiation Recruit M2 Macrophage into the Lung, Leading to Pneumonitis and Pulmonary Fibrosis

Park

Jung

2017

J Radiat Prot Res

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Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods:After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion:Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion:All results show that thoracic irradiation induces to infiltrate various inflammation-related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.

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Modulation of pulmonary fibrosis by IL-13Rα2

Cited by 36 publications

References 34 publications

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

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

Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis

Thoracic Irradiation Recruit M2 Macrophage into the Lung, Leading to Pneumonitis and Pulmonary Fibrosis

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