Mast cell–derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B

Grimbaldeston, Michele A.; Nakae, Susumu; Kalesnikoff, Janet; Tsai, Mindy; Galli, Stephen J.

doi:10.1038/ni1503

Cited by 412 publications

(393 citation statements)

References 50 publications

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“…These antigen-specific IgG 1 antibodies develop, probably by mast-cell-independent mechanisms, in response to the initial exposure to hapten during the sensitization phase of CHS 23 . Thus, in this model, the development of an aspect of the humoral component of the immune response to hapten challenge (the antigen-specific IgG 1 ) results in the generation of a signal (the antigen-IgG 1 immune complexes) that promotes an anti-inflammatory phenotype in the mast cells that are resident at the site of the local reaction (Figure 3h).…”

Section: Discussionmentioning

confidence: 99%

“…The most commonly used animals for such studies are the WBB6F 1 -Kit W/W-v mice and the more recently characterized C57BL/6-Kit W-sh/W-sh mice 1,3,5,13,[22][23][24] .Kit W is a point mutation that produces a truncated c-Kit, which lacks its transmembrane domain and is therefore not expressed on the cell surface; Kit W-v is a (Thr660Met) mutation at the c-kit tyrosine kinase domain that substantially reduces the kinase activity of the receptor; and Kit W-sh is an inversion mutation of the transcriptional regulatory elements upstream of the c-kit transcription start site on mouse chromosome 5 (reviewed in REFS 1,5,13 1,15,22 . WBB6F1-Kit W/W-v mice exhibit several other phenotypic abnormalities, such as macrocytic anaemia, a reduction in the number of bone-marrow and blood neutrophils, sterility, and a marked reduction in number of interstitial cells of Cajal, which are found in the gastrointestinal tract 1,15,22,24,25 .…”

Section: Mast-cell Knock-in Micementioning

confidence: 99%

“…Mast cells and mast-cell derived IL-10 markedly limited the magnitude, and promoted the resolution, of both innate responses to chronic low-dose UVB-irradiation and of CHS responses induced in response to the hapten 2,4-dinitro-1-fluorobenzene (DNFB) or to urushiol, which is the hapten-containing sap of poison ivy or poison oak 23 . Mast-cell derived IL-10 was shown to limit multiple aspects of these responses, including the numbers of granulocytes, macrophages and T cells at the reaction sites, as well as the local tissue swelling, epidermal hyperplasia and, importantly, full thickness epidermal necrosis and ulceration.…”

Section: Negative Immunomodulatory Functions In Vivomentioning

confidence: 99%

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Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

2008

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Section: Discussionmentioning

confidence: 99%

Section: Mast-cell Knock-in Micementioning

confidence: 99%

Section: Negative Immunomodulatory Functions In Vivomentioning

confidence: 99%

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Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

2008

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“…Mast cell-derived IL10 has been reported to limit contact dermatitis and chronic irradiation with ultraviolet B. 28 Similarly, in IgG4-related disease, mast cell production of IL10 may prevent allergic inflammation in the affected organs.…”

Section: Discussionmentioning

confidence: 99%

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

et al. 2014

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IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffinembedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFb1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

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“…Mast cell-derived IL-10 is required to maintain skin homeostasis after exposure to excessive amounts of UVB. 76 In addition, UV-induced IL-10 plays a key role in skin cancer development, as IL-10 -deficient mice are completely protected from developing skin tumors after long-term exposure to carcinogenic UV. 77 More recently, UV-induced vitamin D3 was shown to be one trigger for IL-10 production by dermal mast cells.…”

Section: Discussionmentioning

confidence: 99%

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Byrne

Beaugie

O’Sullivan

et al. 2011

The American Journal of Pathology

101

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The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skininfiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

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Mast cell–derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B

Cited by 412 publications

References 50 publications

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

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