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 3

Increased activation of T cells is observed in the skin and cervical LNs of hCD1Tg HJ1Tg Apoe–/– mice.

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Increased activation of T cells is observed in the skin and cervical LNs...
Dermal and LN cells were isolated from indicated mice at 25 weeks of age, stained with anti-CD45 Abs, and gated on TCRβ+ cells. Cell-surface staining was performed for T cell activation markers. (A and C) Representative FACS plots of the expression of T cell activation markers CD69 and CD44 in the dermis (A) and cervical LNs (C). (B and D) Bar graphs depict the mean + SEM of the percentages of CD69+CD44+ T cells in the dermis (B) and LNs (D) of the mice (n = 5–10). (E) Representative FACS plots of CD5 expression on dermal T cells from indicated mice. (F) Bar graph depicts the MFI of CD5 expression on dermal T cells in different mouse strains (n = 3). ***P < 0.005; **P < 0.01; *P< 0.05. Statistical analyses were performed using 1-way ANOVA followed by Bonferroni’s post-hoc test.