Ultraviolet B Radiation Induces a Transient Appearance of IL-4+ Neutrophils, Which Support the Development of Th2 Responses

Abstract

UVB irradiation can cause considerable changes in the composition of cells in the skin and in cutaneous cytokine levels. We found that a single exposure of normal human skin to UVB induced an infiltration of numerous IL-4+ cells. This recruitment was detectable in the papillary dermis already 5 h after irradiation, reaching a peak at 24 h and declining gradually thereafter. The IL-4+ cells appeared in the epidermis at 24 h postradiation and reached a plateau at days 2 and 3. The number of IL-4+ cells was markedly decreased in both dermis and epidermis at day 4, and at later time points, the IL-4 expression was absent. The IL-4+ cells did not coexpress CD3 (T cells), tryptase (mast cells), CD56 (NK cells), and CD36 (macrophages). They did coexpress CD15 and CD11b, showed a clear association with elastase, and had a multilobed nucleus, indicating that UVB-induced infiltrating IL-4+ cells are neutrophils. Blister fluid from irradiated skin, but not from control skin, contained IL-4 protein as well as increased levels of IL-6, IL-8, and TNF-α. In contrast to control cultures derived from nonirradiated skin, a predominant type 2 T cell response was detected in T cells present in primary dermal cell cultures derived from UVB-exposed skin. This type 2 shift was abolished when CD15+ cells (i.e., neutrophils) were depleted from the dermal cell suspension before culturing, suggesting that neutrophils favor type 2 T cell responses in UVB-exposed skin.

Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines

“…Our experiments indicate that the interaction of widely distributed Fas-expressing DCs with FasL-transfected tumor cells and subsequent secretion of chemokines by DCs may play an important role in this process. Given the established role of neutrophils in T-cell responses, [38][39][40] our data clearly suggest that Fas-ligation on DCs promotes innate and adaptive immunity by enhancing the functions of recruited neutrophils and T cells. Our experiment may provide an explanation for the rejection of FasL-expressing tumor cells by infiltrating neutrophils and the ensuing development of CD8 ϩ T-cell-dependent antitumor immunity.…”

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

“…Neutrophil infiltration is a very early cellular event occurring in response to sunlight, with significant numbers first appearing in human dermis within 10 hours and reaching a maximum by 24 hours after UVB exposure. 56 The majority of these UV-recruited neutrophils home to the dermis 56 where they mediate immune suppression via IL-4 and IL-10 production. 56,79 Between days 3 and 5 after UV exposure, CD11b ϩ IL-10 -producing macrophages start to appear.…”

“…56 The majority of these UV-recruited neutrophils home to the dermis 56 where they mediate immune suppression via IL-4 and IL-10 production. 56,79 Between days 3 and 5 after UV exposure, CD11b ϩ IL-10 -producing macrophages start to appear. 80 Macrophage phenotype can be altered by IL-33 81 suggesting that UV-induced IL-33 may also affect macrophage function, although further studies are required to determine whether this is the case.…”

Cutting Edge: Loss of TLR2, TLR4, and TLR5 on Langerhans Cells Abolishes Bacterial Recognition

“…Epidermal and dermal cell suspensions were obtained from residual skin obtained from plastic surgery as described previously (11,12). Overnight incubation at 4°C in 0.2% dispase II (Boehringer Mannheim) enabled separation of epidermis and dermis, whereafter epidermal sheets were incubated in 0.25% trypsin solution (5 min at 37°C; Invitrogen Life Technologies), and dermal sheets in IMDM containing 0.2% collagenase D (Boehringer Mannheim), 40 U/ml DNase I (Boehringer Mannheim), and 2% FCS for 2 h at 37°C to yield single cells.…”