Background/Purpose: Proper function of lymphatic vessels is needed to limit the magnitude and duration of tissue inflammation. Chronic inflammatory states such as obesity and psoriasis are associated with lymphatic dysfunction, but lymphatics in lupus models have not been well characterized. SLE patients are photosensitive, developing inflammatory skin lesions upon exposure to even ambient ultraviolet radiation (UVR). We hypothesized that lymphatic dysfunction may contribute to photosensitivity in lupus.

Methods: 8-10 week old MRL/MpJ-Fas^lpr/lpr (lpr) mice and age-/sex-matched MRL controls were evaluated at baseline, and after exposure to UVR. The source of UVR was a set of 4 FS40T12 sunlamps emitting UVA and UVB at 40:60 ratio. The overall dose of the total radiation ranged from 2000-2500 J/m². Lymphatic function was assessed with an intradermal injection of 1µL of 2% evans blue (EB) to the ear, followed by measurement of EB concentration in the draining auricular lymph node (LN). Flow cytometry of ears and auricular LN allowed quantification of resident cell populations, and local mRNA expression of vascular endothelial growth factor-C (VEGF-C) was evaluated by real-time PCR. Mann-Whitney U test was used to compare the groups; data is presented as mean ± SE, with a two-tailed p-value of <0.05 considered significant.

Results: At baseline, auricular LNs of lpr mice are bigger and are about 10-fold more cellular than controls (21523860 ± 3861631 cells vs. 2184360 ± 464267 cells, respectively; p=0.008), but there is no compensatory increase in dermal lymphatic endothelial cells (LEC) to allow for an increase in local lymphatic transit to the LN (8918 ± 2142 LEC in lpr vs. 6106 ± 1023 LEC in controlsy; p=0.421). Accordingly, already at baseline, the effective flow of EB from the ear to the LN in lpr mice is only 44% that of controls, when accounting for the weight of the LN. Importantly, post-UVR, EB drainage in lpr mice is reduced to only 10% that of controls, and this value persists both 1 week after UVR and 1 month later. Interestingly, we have observed that at the peak of local inflammation that occurs at around 7 days post-UVR, VEGF-C mRNA levels are suppressed in both lpr and MRL strains, compared with non-UV exposed controls.

Conclusion: Dermal lymphatic network of lupus models have never been characterized, despite evidence for a major role of lymphatics in the regulation of chronic inflammation. Here we provide indications to impaired local lymphatic drainage in the lpr lupus strain, which can lead to reduced inhibitory signals arriving at the overactive lymph node from the lymphatic circulation, contributing to the unchecked inflammation known to occur in SLE. UVR is shown to further impair local lymphatics, particularly in the lupus strain, possibly through suppression of VEGF-C production.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dermal-lymphatic-dysfunction-and-photosensitivity-in-the-mrl-lpr-lupus-model/