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 8

Psoriatic patients have an increased frequency of autoreactive group 1 CD1–restricted T cells.

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Psoriatic patients have an increased frequency of autoreactive group 1 C...
Psoriatic and normal skin biopsies were stained with Abs against CD1a, CD1b, and CD1c. Scale bars: 100 μm. (B) Bar graph depicts number of CD1a-, CD1b-, and CD1c-positive cells/mm2 (mean + SEM) (n = 3); skin biopsies were derived from psoriatic patients who were hyperlipidemic. (C) K562 alone and K562 CD1 transfectants were cocultured with human T cells (n = 9) that were stimulated twice with autologous mo-DCs followed by IL-2 ELISPOT assay. (D) PBMCs from psoriatic and normal individuals were stained with untreated CD1b tetramers or CD1b tetramers loaded with PE and PG (n = 5 for psoriatic patients; n = 8 for normal individuals). Cells depicted on the FACS plots were first gated on the lymphocyte population and then on CD19– cells. (E) Bar graph depicts mean ± SEM of the percentages of tetramer-positive cells. ***P < 0.005; **P < 0.01; *P < 0.05, Mann-Whitney U test.