hcd1tg/hj1tg/ ApoE-/- hcd1tg/hj1tg/ ApoE+/+

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1 ApoE+/+ ApoE-/- ApoE-/- H&E (1x) Supplementary Figure 1. No obvious pathology is observed in the colon of diseased ApoE-/me. Colon samples were fixed in 1% formalin and laid out in Swiss rolls for paraffin embedding. Paraffin sections were cut and stained with H&E to examine the tissue architecture. Scale bars represent 1 µm.

2 % CD4 + Foxp Cerval Lymph Node % CD4 + Foxp3 + 1 Skin (dermis) ApoE +/+ Supplementary Figure. ApoE +/+ and me have comparable numbers of FoxP3 + regulatory T cells. Cells isolated from the (A) cerval lymph nodes and () dermis were stained intracellularly with Foxp3 and gated on CD45 + TCRb +. Subsequently, the CD4 and Foxp3 positive Treg cell population was examined (n=3-5). P <.5; P <.1; P<.5; n.s. = not signifant. Statistal analysis was performed using One-Way ANOVA followed by onferroni post-hoc test.

3 Dermis Epidermis ApoE +/ ApoE +/ CD11b CD11c CD7 CD11c Gated on CD11b + CD11c - cells Gated on CD7 + CD11c + cells Gated on CD11b + CD11c + cells C ApoE +/+ Epidermis Gated on CD11b - CD11c + cells Keratinocytes Hair follle stem cells Supplementary Figure 3. is expressed on a subset of dermal dendrit cells. (A) Dermal cells were isolated and stained with mabs against CD45, CD11b, CD11c, and. expression on CD11b + CD11c -, CD11b + CD11c + and CD11b - CD11c + populations were analyzed by flow cytometry. () Epidermal cells were isolated and stained with mabs against CD45, CD7, CD11c and. expression on CD7 + CD11c + population (Langerhans cells) was analyzed by flow cytometry by gating on CD45 + cells. (C) expression on hair follle stem cells and keratinocytes was determined by gating on CD45 - cells and then on integrin a6 and b1 double positive cells. Subsequently, CD34 + Sca-1 - hair follle stem cells or CD34 - Sca-1 + epidermal keratinocytes were output for expression. Data shown are representative of at least experiments for all figure panels.

4 nmol/mg dry lipid weight c ApoE +/+.6 5 Fold Change Skin Liver /ApoE C 34 LN1-7 reactivity to lipids IL- Fold Change 3 4 with Supplementary Figure 4. Fatty acids do not show preferential accumulation in the skin of me and reactivity of lipids to a second mouse -autoreactive hybridoma. Total lipid was extracted from skin and liver tissues of indated me, weighed and analyzed by gas chromatography. (A) Fatty acid species in the skin of diseased and healthy ApoE +/+ me (n=3) were quantified. () Ratio of fatty acids from diseased over healthy me in the skin and liver. (C) Polar phospholipids (PL), cholesterol (Chol) and fatty acid mixtures (FA1: saturated and monounsaturated and FA: polyunsaturated) were loaded on to protein and incubated with LN1-7 T cell hybridoma for 4 h. IL- in the supernatant was measured by ELISA. Data are representative of at least experiments. P <.1; P<.5. Statistal analysis was performed using Student s t-test.

5 Supplementary table 1: Oligonucleotide primers used in the study Name For genotyping HJ1a F HJ1a R Sequence (5'-3') TGACACCTGCTCAGTTCTTGTGC TAGCTTGTTCCCTGCACTTGG CD1c F CD1c R CAGAAACTGCAGAAACAGCA GATGGGTGAAAAGAGGTGAAA ApoE WT ApoE Common ApoE Mutant TGTGACTTGGGAGCTCTGCAGC GCCTAGCCGAGGGAGAGCCG GCCGCCCCGACTGCATCT For RT-PCR IL-18Ra F IL-18Ra R TCACCGATCACAAATTCATGTGG TGGTGGCTGTTTCATTCCTGT IL-1Rb1 F IL-1Rb1 R TGCCGCTACTTCTCCTCAG ACTTCATGGTTCGGTTCCCAA TLR9 F TLR9 R ATGGTTCTCCGTCGAAGGACT GAGGCTTCAGCTCACAGGG S1a7 F S1a7 R GTA CTC AGG TCA TGG TTC TG GGT ATT CAA GCA AGG TAT CAC S1a8 F S1a8 R GGA GTT CCT TGC GAT GGT GAT TCC TTG TGG CTG TCT TTG TGA b-actin F b-actin R CTT CTT TGC AGC TCC TTC GTT AGG AGT CCT TCT GAC CCA TTC IL-17F F IL-17F R TGC TAC TGT TGA TGT TGG GAC AAT GCC CTG GTT TTG GTT GAA IL-17A F IL-17A R ACT TTC AGG GTC GAG AAG A TTC TGA ATC TGC CTC TGA AT IL- F IL- R ATG AGT TTT TCC CTT ATG GGG AC GCT GGA AGT TGG ACA CCT CAA GM-CSF F GM-CSF R GGC CTT GGC AGC ATG TAG AGC GGA GAA CTC GTT AGA GAC GAC TT TNF-a F TNF-a R CCA CCA CGC TCT TCT GTC T GGC ACC ACT AGT TGG TTG T IL-6 F IL-6 R CTT GGG ACT GAT GCT GGT GAC A GCC TCC GAC TTG TGA AGT GGT A TGb1 F TGb1 R CTC CCG TGG CTT CTA GTG C GGCC TTA GTT TGG ACA GGA TCT G IL-4 F IL-4 R AAC TCC ATG CTT GAA GAA GAA CTC CCA GGA AGT CTT TCA GTG ATG TG IL-3 F IL-3 R CCA TTA GGA CTT GTG CTG TTC T CCA AGG GCT CGA GAC TTT ATT C IFN-g F IFN-g R TCA AGT GGC ATA GAT GTG GAA GAA TGG CTC TGC AGG ATT TTC ATG HJ1Vb F HJ1Vb R ATC TCT TCC CGG TGC TGA TT TCT GGT TCC TGA GCC AAA AT