Background: Psoriasis is a common autoimmune disease that affects 3% of the adult population. Hypertension is common in humans with Psoriasis and T cells are known to contribute to both conditions. Isolevuglandins (IsoLGs) are peroxidation products of arachidonic acid that rapidly adduct to lysine, forming neoantigen peptides which are presented by class 1 major histocompatibility complexes (MHCs). These IsoLG-adducted peptides stimulate T cell activation, cytokine production and ultimately lead to disease manifestations. We recently identified 4 peptides that when IsoLG-adducted are antigenic in hypertension. Hypothesis: IsoLG-specific T cells are similar between hypertension and psoriasis. Methods: We employed an experimental model of psoriasis caused by keratinocyte-specific overexpression of Tie2 (KC-Tie2, n = 7) and employed littermate controls (n = 7). Mice were studied at 10 to 12 weeks of age. We created fluorescently labeled probes composed of the murine class I MHC H2-D b complexed with IgG and loaded with the pro-hypertensive antigenic peptide cadherin 16 (CDH16), IsoLG adducted (Figure 1A). This was employed in flow cytometric analysis of skin and spleen of KC-Tie2 and littermate control mice. Results: Using radiotelemetry, we confirmed that KC-Tie2 mice develop modest blood pressure elevations by 10-12 weeks of age (daytime systolic pressure 111 ± 3 in KC-Tie2 vs 101 ± 2 mmHg in littermate controls p < 0.007). In the skin of littermate controls, only 2 ± 1 % of total CD8+ T cells were recognized by the IsoLG-adducted CDH16/H2-D b probe, while in the inflamed skin of KC-Tie2 mice, 8 ± 2% of CD8+ T cells were specific for this peptide (p < 0.004, Figure 1B). In the spleen, virtually no IsoLG-adducted CDH16 specific CD8+ T cells were present (Figure 1C). The non-adducted CDH16/H2-D b probe did not bind to T cells in any tissue examined. Conclusions: T cells specific for IsoLG adducts that form in hypertension are also markedly increased in the inflamed skin of mice with experimental psoriasis. Unlike hypertension, in which these cells are also present in the spleen, we observe virtually no IsoLG-specific splenic T cells in psoriasis, suggesting specificity of T cell localization between the two conditions. These observations might explain the increased prevalence of hypertension in patients with psoriasis.
Chen et al. (Mon,) studied this question.