Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: Could it be related to a different cytokine microenvironment?

Moretti, Silvia; Spallanzani, Adelina; Pinzi, Cinzia; Prignano, Francesca; Fabbri, Paolo

doi:10.1111/j.1600-0560.2006.00616.x

Cited by 37 publications

(28 citation statements)

References 19 publications

(54 reference statements)

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“…They also activate CD8 + T cells and cause melanocyte destruction [28]. The ratio of CD4 + T cells to CD8 + T cells has been reported to vary from 1:1 to 1:3 [27,28,29]. This study, however, revealed a predominance of CD8 + T cells; CD4 + T cells were rarely observed.…”

Section: Discussioncontrasting

confidence: 49%

Foxp3<sup>+</sup> Regulatory T Cells Are Increased in the Early Stages of Halo Nevi: Clinicopathological Features of 30 Halo Nevi

Park¹,

Jin²,

Choi³

et al. 2012

Dermatology

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Background: There have been few clinical studies of the role of regulatory T cells (Tregs) in halo formation of halo nevus. Objective: To evaluate the clinicopathologic features and the presence of Tregs in halo nevi. Methods: We analyzed 30 halo nevi and performed immunohistochemical analysis using antibodies against CD4, CD8, CD25 and Foxp3. We also performed double immunohistochemical staining for Foxp3 and CD25. Results: We found significant increases in Foxp3⁺ Tregs, and the shorter the halo nevus duration, the more Foxp3⁺ Tregs were detected. Also, the ratio of Foxp3 to CD8 T cells was increased in early stages of halo nevi. Double immunohistochemical staining suggested that the Tregs in the halo nevi were CD25⁺Foxp3⁺ T cells. Conclusions: Foxp3⁺ Tregs were greatly increased in the halo nevi. The shorter the halo nevi duration, the more Foxp3⁺ Tregs were involved in the earlier developmental stages of halo nevi.

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Section: Discussioncontrasting

confidence: 49%

Foxp3<sup>+</sup> Regulatory T Cells Are Increased in the Early Stages of Halo Nevi: Clinicopathological Features of 30 Halo Nevi

Park¹,

Jin²,

Choi³

et al. 2012

Dermatology

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“…The prototype of regressing melanocytic nevus is a ‘halo’ nevus which is usually unassociated with a melanoma 13 . Moretti et al 14 observed that the T‐cell infiltrate and cytokine milieu is distinct in regressed melanoma (in which melanocyte disappearance is coupled with fibrosis) when compared with regressing halo nevi (in which melanocyte disappearance elicits inconspicuous fibrosis). Areas of regressed melanoma contain a predominance of CD4‐positive T cells, while halo nevi are rich in CD8‐positive cells.…”

Section: Discussionmentioning

confidence: 99%

A lack of significantly increased incidence of regression in second primary melanomas does not support an ‘immunization effect’

et al. 2010

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“…Both IL-6 and TGF-β are well-known fibrotic cytokines, and numerous fibrotic skin conditions are characterized by the coexpression of these cytokines. For instance, skin surrounding regressing melanoma is highly fibrotic and displays increased expression of IL-6 and TGF-β levels, whereas the skin around halo naevi is not fibrotic and does not show elevated expression of these cytokines 80. Damage by ionizing radiation also causes fibrotic changes that appear to be linked to IL-6 and TGF-β expression (review81).…”

Section: Discussionmentioning

confidence: 99%

Interleukin (IL)-6 modulates transforming growth factor-β expression in skin and dermal fibroblasts from IL-6-deficient mice

Luckett-Chastain

Gallucci

2009

British Journal of Dermatology

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Summary Background Interleukin (IL-6) and transforming growth factor (TGF)-β have been shown to play a role in skin development and maintenance. Objectives A link between these two cytokines has yet to be identified and therefore in this study we investigated the modulation of TGF-β1 and TGF-β type 2 receptor (TGF-βR2) by IL-6 in skin. Methods An IL-6 knockout (IL-6KO) fibroblast-populated lattice model and intradermal injections of IL-6 into unwounded IL-6KO mice were used to investigate the direct effects of IL-6 treatment on TGF-β and TGF-βR2 expression and to determine the signalling mechanism. In addition, IL-6KO and C57BL/6 control mice were wounded by a 4-mm punch biopsy to monitor expression of TGF-β1 and TGF-βR2 within a wound over time. The expression of TGF-β1 and TGF-βR2 was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistology. Results Recombinant IL-6 treatment of IL-6KO lattices and intradermal injections of IL-6 showed a significant induction of TGF-β1 mRNA and protein, with TGF-β1 expression localized in the dermis, while TGF-βR2 expression was primarily in the epidermis in IL-6KO mice. During healing, the expression of TGF-β1 and TGF-βR2 mRNA was significantly greater in unwounded and 7-day-old wounds from wild-type mice; however, protein expression did not differ. Treatment with signal transduction inhibitors indicated that IL-6 modulates TGF-β through a mitogen-activated protein kinase/extracellular signal-regulated kinase (Mapk/Erk)-dependent mechanism. Conclusion These studies indicate that IL-6 has the ability to modulate the expression of TGF-β and TGF-βR2 to varying degrees in the skin, which may provide a possible mechanism for defining the role of IL-6 in skin maintenance and a new association of IL-6 with TGF-β in pathologies associated with fibrosis.

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Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: Could it be related to a different cytokine microenvironment?

Cited by 37 publications

References 19 publications

Foxp3<sup>+</sup> Regulatory T Cells Are Increased in the Early Stages of Halo Nevi: Clinicopathological Features of 30 Halo Nevi

Foxp3<sup>+</sup> Regulatory T Cells Are Increased in the Early Stages of Halo Nevi: Clinicopathological Features of 30 Halo Nevi

A lack of significantly increased incidence of regression in second primary melanomas does not support an ‘immunization effect’

Interleukin (IL)-6 modulates transforming growth factor-β expression in skin and dermal fibroblasts from IL-6-deficient mice

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