Background/Purpose:

Two-thirds of systemic lupus erythematosus (SLE) patients are sensitive to sunlight and artificial light. Ultraviolet (UV) B light induces sterile inflammation in the skin and results in both localized cutaneous and systemic disease, including lupus nephritis. The precise mechanisms of photosensitivity-triggered systemic reactions in SLE are unknown.

Methods:

Mice (C57BL/6J, 3-4mo female and male) were exposed to a single dose of UVB (500mJ/cm2). Individual mice were euthanized on 1, 2, or 6 days after UVB and perfused with saline; non-irradiated age and sex matched mice were used as controls. Immune cells isolated from the skin, bone marrow (BM), blood, spleen, lung, and kidney were profiled and neutrophil phenotype characterized by flow cytometry (FC). Cytokine and chemokine gene expression in skin was evaluated by QPCR. Tissue apoptotic cells and IgG were examined by immunofluorescence and kidney pathology evaluated by PAS staining.

Results:

Following skin UVB exposure, the decline in the number of BM neutrophils associated with an increase in blood and skin neutrophil numbers at days 1-2 (d1-2). Of considerable interest, neutrophil numbers also increased in the lung, spleen, and kidney, with a peak on d6 post-UVB. While a similar migration pattern was seen in both male (M) and female (F) mice, the dynamic of the immune response was sex-dependent. Neutrophils in F mice infiltrated the irradiated skin more rapidly (d1 in F vs. d2 in M), a response reflected by faster gene induction of neutrophil chemoattractants (G-CSF, KC, LIX) and inflammatory cytokines (IL1b, IL6, IL33) in the F mice. Significantly higher levels of circulating neutrophils were found on d6 following UVB in F, relative to their M counterparts. In both M and F mice, immediately following UVB, circulating neutrophils expressed increased CXCR2, while later on (d6) CXCR4^hi neutrophils were detected in the kidney and the BM and ICAM1^hiCXCR1^lo neutrophils were found in the kidney, lung, BM, and blood.

To investigate the effects of UV exposure in a lupus prone model we studied Sle1.Mfge8-/-C3-/- mice. These mice were particularly sensitive to UVB, with persistent skin lesions and increased accumulation of apoptotic debris and IgG in the skin. UV exposure in this lupus model led to nephritis and premature death. Preliminary data indicate that UVB exposure resulted in glomerular antibody deposition associated with CXCR4^hi and ICAM1^hiCXCR1^lo neutrophil infiltration.

Conclusion:

Our findings provide several novel insights into the neutrophil response to UVB exposure: i) localized skin sterile injury triggers neutrophil migration to peripheral organs, including the kidney, ii) the dynamics of neutrophil infiltration into the skin are sex-dependent, and iii) presence of CXCR4^hi and ICAM1^hiCXCR1^lo neutrophil populations in peripheral organs suggests that a subset of activated skin-infiltrating neutrophils has migrated to distal organs, possibly via reverse transmigration. Evidence of a similar neutrophil population in a UV-sensitive lupus model associated with kidney injury strongly suggests neutrophil involvement in UV-triggered systemic pathology in SLE.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/neutrophil-response-to-ultraviolet-light-in-normal-and-lupus-conditions/