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

Abstract

Allergic contact dermatitis, such as in response to poison ivy or poison oak, and chronic low-dose ultraviolet B irradiation can damage the skin. Mast cells produce proinflammatory mediators that are thought to exacerbate these prevalent acquired immune or innate responses. Here we found that, unexpectedly, mast cells substantially limited the pathology associated with these responses, including infiltrates of leukocytes, epidermal hyperplasia and epidermal necrosis. Production of interleukin 10 by mast cells contributed to the anti-inflammatory or immunosuppressive effects of mast cells in these conditions. Our findings identify a previously unrecognized function for mast cells and mast cell–derived interleukin 10 in limiting leukocyte infiltration, inflammation and tissue damage associated with immunological or innate responses that can injure the skin.

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Figure 1: Mast cells and mast cell–derived IL-10 can limit the tissue swelling associated with CHS responses to urushiol or DNFB.
Figure 2: Mast cells and mast cell–derived IL-10 can limit the skin pathology associated with CHS responses to DNFB.
Figure 3: Mast cells and mast cell–derived IL-10 can limit the number of leukocytes and epidermal thickening at sites of CHS responses to DNFB.
Figure 4: Mast cell FcRγ can limit the tissue swelling associated with CHS responses to urushiol or DNFB.
Figure 5: Mast cells and mast cell–derived IL-10, but not mast cell FcRγ, can limit the tissue swelling, epidermal thickening and leukocyte recruitment associated with chronic low-dose UVB irradiation.
Figure 6: Mast cells and mast cell–derived IL-10 can limit the pathology associated with chronic low-dose UVB irradiation of ear skin.

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Acknowledgements

We thank Z.-S. Wang, A. Xu, C. Liu, D. Guthrie and J. Ling for help with histological processing and analysis of tissues; C.-C. Chen for assistance with and advice on flow cytometry; A. Del Grosso (US Food and Drug Administration) for purified urushiol from poison oak (Toxicodendron diversilobum); D. Segal (National Institutes of Health) for mouse U7.6 hybridoma cells producing IgG1 mAb to DNP; M. Kiniwa (Taiho Pharmaceutical) for mouse 3B2E6 hybridoma cells producing IgG1 mAb to ovalbumin; and F.-T. Liu (University of California-Davis) and D.H. Katz (Avanir Pharmaceuticals) for IgE mAb to DNP generated from ascites induced by the hybridoma H1-DNP-ε26. Breeding pairs of B6-KitW-sh/+ mice and BALB/c-Fcer1a−/− mice were provided by P. Besmer (Memorial Sloan-Kettering Cancer Center) and J.-P. Kinet (Beth Israel Deaconess Medical Center), respectively.

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M.A.G. did all experiments and together with S.J.G. conceived and designed the study, interpreted the findings and wrote the manuscript; S.N. provided expertise for flow cytometry; J.K. helped with some experiments; and S.N., J.K. and M.T. assisted with interpretation of the findings and the writing of the manuscript.

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Correspondence to Stephen J Galli.

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Grimbaldeston, M., Nakae, S., Kalesnikoff, J. et al. Mast cell–derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 8, 1095–1104 (2007). https://doi.org/10.1038/ni1503

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