Dermal Mast Cells Determine Susceptibility to Ultraviolet B–induced Systemic Suppression of Contact Hypersensitivity Responses in Mice

Abstract

Different strains of mice have varying susceptibilities to ultraviolet radiation (UV) of wavelength 280–320 nm (UVB) for 50% suppression of systemic contact hypersensitivity (CHS) responses. Prevalence of histamine-staining dermal mast cells in different strains of mice (C57BL/ 6J, DBA/2, BALB/c) correlated directly with their susceptibility to UVB-induced systemic immunosuppression. BALB/c mice carrying Uvs1, a major locus for susceptibility to UV-induced immunosuppression, contained greater numbers of dermal mast cells than BALB/c mice of the same parental origin. Strains of mice that were differentiated on their susceptibility to UVB-induced downregulation of systemic CHS responses were similar in their susceptibility to histamine-induced immunomodulation. Histamine, but not UVB irradiation, decreased systemic CHS responses in mast cell–depleted mice (W f/W f). Reconstitution of the dorsal skin of W f/W f mice with bone marrow–derived mast cell precursors from nonmutant mice rendered the mice susceptible to UVB irradiation for systemic suppression of CHS responses. UVB irradiation did not suppress delayed type hypersensitivity responses to allogeneic spleen cells in W f/W f mice. In contrast, UV irradiation suppressed CHS responses in W f/W f mice when hapten was applied to the irradiated site. This study demonstrates that dermal mast cells are necessary for the induction of systemic suppression of CHS responses by UVB radiation, and suggests that mast cell– derived histamine is one component of this UVB-induced systemic immunosuppression.

Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2Areceptor

“…Whether cis-UCA binding to 5-HT 2A receptors expressed on T and B cells is responsible for IL-10 production remains to be seen. It is also well known that mast cell activation is critical for UV-and͞or cis-UCA-induced immune suppression (30,31). Kahlil et al (41) report that cis-UCA does not directly cause degranulation of mast cells, but rather stimulates neuropeptide release from peripheral nerves, which in turn activates mast cells.…”

“…In our experiments, serotonin͞ cis-UCA͞UV exposure was given 5 days before immunization and 15 days before challenge. We propose that serotonin or cis-UCA given well before challenge activates processes known to be critical for UV-and cis-UCA-induced immunosuppression, such as mast cell activation (30,31) and the secretion of antiinflammatory cytokines (14) that normally serve to dampen hypersensitivity reactions. UV exposure maybe acting in vivo to accelerate these normal feedback mechanisms, thereby promoting immune suppression.…”

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

“…Mast cells represent potential sources of many mediators that can enhance or suppress the development, survival, proliferation, migration, maturation, or function of immune cells (reviewed in REFS [1][2][3][5][6][7][8]13,[16][17][18]21,30,31,43,44,[46][47][48][49][50][51][52][53][54][55][56]. Some individual mediators, such as histamine, can have both positive and negative immunomodulatory effects.…”

“…Hart et al 49 showed that the ability of ultraviolet B (UVB) irradiation of the skin to induce systemic immunosuppression of contact hypersensitivity (CHS) responses to the hapten 2,4,6-trinitrochlorobenzene was markedly reduced in (C57BL/6 × DBA/2)F1-Kit W-f/W-f mice but was restored following mast-cell knockin. Several lines of evidence suggested that histamine was a major mediator of this UVBinduced, mast cell-dependent effect.…”

“…Although histamine can be made by basophils and other immune cells, as well as by mast cells, mast cells represent a major source of histamine in the normal skin of mice. Mast cells were probably also responsible for the finding that UVB irradiation suppressed delayed-type hypersensitivity (DTH) responses to allogeneic spleen cells in Kit W-f/+ mice (which contain dermal mast cells) but not in Kit W-f/W-f mice (which do not contain dermal mast cells) 49 .…”