Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin requires mast cell degranulation.
The deleterious effects of ultraviolet B radiation (UVR) on cutaneous immunity are mediated in part by cytokines released from cutaneous cells following radiation exposure. On the one hand, TNF-alpha has been advocated as the primary mediator of failed contact hypersensitivity induction, and, on the other hand, IL-10 has been held responsible for tolerance. While keratinocytes exposed to UVR have been found to produce both TNF-alpha and IL-10, there is reason to question whether these major cellular constituents of the epidermis are the relevant source of immunomodulatory cytokines after UVR. Dermal mast cells also produce TNF-alpha and IL-10, and we have recently reported that mast cell-derived TNF-alpha is required for UVR-induced impairment of CH induction. In this study, we have examined whether mast cells are also a relevant source of IL-10 in UVR-dependent tolerance. We found that (a) UVR fails to induce tolerance in mast cell-deficient mice, and (b) that tolerance occurs if mast cells are triggered to degranulate after ligation of the IgE receptor. Both types of tolerance were neutralized with anti-IL-10 antibodies, are hapten specific, and are associated with regulatory lymphoid cells. We conclude that mast cells are required in UVR-induced tolerance and may be one of the major sources of IL-10 that mediates the tolerance induced by acute, low-dose UVR.
Alard
P
P
Schepens Eye Research Institute, Department of Dermatology, Harvard Medical School, Boston, USA.
Kurimoto
I
I
Niizeki
H
H
Doherty
J M
JM
Streilein
J W
JW
D000276:Adjuvants, Immunologic; D000818:Animals; D015550:Cell Degranulation / Q000276:immunology / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology; D006636:Histamine Release / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology*; D011829:Radiation Dosage; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D010081:Oxazolone; D007073:Immunoglobulin E; D010853:Picryl Chloride