CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice
Sreya Bagchi, … , Johann E. Gudjonsson, Chyung-Ru Wang
Sreya Bagchi, … , Johann E. Gudjonsson, Chyung-Ru Wang
Published May 2, 2017
Citation Information: J Clin Invest. 2017;127(6):2339-2352. https://doi.org/10.1172/JCI92217.
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Research Article Autoimmunity Immunology

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

Abstract

A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that expresses human CD1b and CD1c molecules (hCD1Tg) as well as a CD1b-autoreactive TCR (HJ1Tg) in the ApoE-deficient background (hCD1Tg HJ1Tg Apoe–/– mice) to determine the role of CD1-autoreactive T cells in hyperlipidemia-associated inflammatory diseases. We found that hCD1Tg HJ1Tg Apoe–/– mice spontaneously developed psoriasiform skin inflammation characterized by T cell and neutrophil infiltration and a Th17-biased cytokine response. Anti–IL-17A treatment ameliorated skin inflammation in vivo. Additionally, phospholipids and cholesterol preferentially accumulated in diseased skin and these autoantigens directly activated CD1b-autoreactive HJ1 T cells. Furthermore, hyperlipidemic serum enhanced IL-6 secretion by CD1b+ DCs and increased IL-17A production by HJ1 T cells. In psoriatic patients, the frequency of CD1b-autoreactive T cells was increased compared with that in healthy controls. Thus, this study has demonstrated the pathogenic role of CD1b-autoreactive T cells under hyperlipidemic conditions in a mouse model of spontaneous skin inflammation. As a large proportion of psoriatic patients are dyslipidemic, this finding is of clinical significance and indicates that self-lipid–reactive T cells might serve as a possible link between hyperlipidemia and psoriasis.

Authors

Sreya Bagchi, Ying He, Hong Zhang, Liang Cao, Ildiko Van Rhijn, D. Branch Moody, Johann E. Gudjonsson, Chyung-Ru Wang

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Figure 1

hCD1Tg HJ1Tg Apoe–/– mice spontaneously develop skin inflammation.

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hCD1Tg HJ1Tg Apoe–/– mice spontaneously develop skin inflammation. (A) M...
(A) Mice were weighed beginning at 2.5 months of age up to 5.5 months of age. Percentage change in body weight was calculated over the time period (n = 4–10). (B) Mice were monitored from 20 to 25 weeks for the development of dermatitis and percentages of incidence recorded (left); epidermal thickness was also quantified (right; n = 11–14). (C and D) Representative H&E (C) and Ki67 (D) staining of skin sections from 6-month-old mice. Scale bars: 100 μm. (E) mRNA analysis of S100a proteins in the skin of indicated mice (n = 3–5). (F) Representative oil red O–stained sections from aortic root of Apoe–/– and hCD1Tg HJ1Tg Apoe–/– mice (left panel) are shown, and bar graph depicts the mean + SEM of aortic root plaque area from indicated mice (n = 8–9). ***P < 0.005; **P < 0.01; *P < 0.05. Statistical analyses were performed using 1-way ANOVA followed by Bonferroni’s post-hoc test for 3-group comparisons and Student’s t test for 2-group comparisons.