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Cutting Edge: ABIN-1 Protects against Psoriasis by Restricting MyD88 Signals in Dendritic Cells

Joseph A. Callahan, Gianna E. Hammer, Alexander Agelides, Bao H. Duong, Shigeru Oshima, Jeffrey North, Rommel Advincula, Nataliya Shifrin, Hong-An Truong, Jonathan Paw, Julio Barrera, Anthony DeFranco, Michael D. Rosenblum, Barbara A. Malynn and Averil Ma
J Immunol July 15, 2013, 191 (2) 535-539; DOI: https://doi.org/10.4049/jimmunol.1203335
Joseph A. Callahan
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Gianna E. Hammer
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Alexander Agelides
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Bao H. Duong
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Shigeru Oshima
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Jeffrey North
†Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143; and
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Rommel Advincula
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Nataliya Shifrin
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Hong-An Truong
†Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143; and
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Jonathan Paw
†Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143; and
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Julio Barrera
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Anthony DeFranco
‡Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143
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Michael D. Rosenblum
†Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143; and
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Barbara A. Malynn
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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Averil Ma
*Department of Medicine, University of California, San Francisco, San Francisco, CA 94143;
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  • FIGURE 1.
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    FIGURE 1.

    ABIN-1 expression in DCs is necessary to preserve immune homeostasis. (A) Flow cytometric quantitation of MHC class II+CD11chi cDCs and MHC class II+CD11cdimB220+ pDCs in spleens from indicated mice. (B) Spleens from indicated mice. (C) Flow cytometric analyses of myeloid, T cell, and B cell splenic subpopulations. (D) Quantitation of naive (CD44lo) and memory phenotype (CD44hi or m.p.) T cells. Error bars represent SEM. Open bars indicate ABIN-1+/+ CD11c-Cre+ mice; shaded bars indicate control ABIN-1fl/fl CD11c-Cre+ mice. Data are representative of five to six pairs of 8- to 16-wk-old mice in three to seven independent experiments. *p < 0.05 by Student t test.

  • FIGURE 2.
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    FIGURE 2.

    ABIN-1 restricts MyD88-dependent signals in DCs. (A) Spleen mass of indicated genotypes. (B) Number of myeloid cells in spleens of indicated mice determined by flow cytometry. (C and D) Number of memory phenotype CD4+ (C) and CD8+ (D) T cells in pooled axillary, brachial, and inguinal lymph nodes. All mice are CD11c-Cre+. Error bars represent SEM. All data are representative of three independent experiments. *p < 0.05 by Student t test.

  • FIGURE 3.
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    FIGURE 3.

    ABIN-1 restricts IMQ responses in DCs and prevents experimental psoriasis. (A) Clinical scores of IMQ-induced skin inflammation in ABIN-1fl/fl CD11c-Cre+ and ABIN-1+/+ CD11c-Cre+ (control) mice at indicated days of IMQ treatment. (B–G) H&E-stained sections of back skin of mice of indicated genotypes from areas treated with IMQ. Epithelial layer (epi) is indicated by brackets (B–G). Epidermal hyperplasia (thickening of epidermal layer) is evident in ABIN-1fl/fl mice (C, E, G) compared with ABIN-1+/+ mice (B, D, F). In (C), (E), and (G), open arrows show hyperkeratotic scaling. In (E), broad areas of hypogranulosis (abnormal loss of purple keratohyaline granules in the skin’s granular layer) are indicated by closed arrows. In (G), neutrophils (blue arrow) and parakeratosis (abnormal retention of nuclei in the outermost layer of skin, green arrow) are shown in Munro’s microabscess (dotted boxed area). Scale bar, 0.1 mm for (D)–(G). Scale bar, 0.5 mm for (B) and (C). (H) ELISA and multiplex Luminex analyses of cytokine production from BMDCs after treatment with the indicated doses of IMQ. (I) Numbers of CD3+ and CD4+ T cells from skin-draining lymph nodes from IMQ-treated mice of indicated genotypes. Numbers of Th17 (CD4+IL-17+), TCRγ/δ+ (CD3+GL-3+), and Th1 (CD4+IFN-γ+) T cells from skin-draining lymph nodes from IMQ-treated mice. Distinct Th2 (CD4+IL-4+) populations were not detected. All mice in (A)–(G) and (I) are CD11c-Cre+ radiation chimera. All data are representative of three to seven independent experiments. Error bars represent SD. *p < 0.05 by Student t test.

  • FIGURE 4.
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    FIGURE 4.

    ABIN-1 restricts MyD88 signals in DCs to prevent IMQ-induced psoriasis. (A) Clinical skin inflammation scores in the indicated genotypes of mice at the indicated days of IMQ treatment. (B) H&E-stained sections of back skin of mice of indicated genotypes after treatment. Epithelial layer denoted by brackets and “epi.” Note that skin inflammation in ABIN-1fl/flMyD88+/+ mice is abrogated in ABIN-1fl/flMyD88fl/fl mice. All mice are CD11c-Cre+. Error bars represent SD. *p < 0.05 by Student t test. Scale bar, 0.1 mm. Data are representative of three independent experiments.

Additional Files

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    • Supplemental Figures 1-2 (PDF, 167 Kb) - Description:
      Supplemental Figure 1: Generation of loxP flanked ABIN-1 (tnip1) allele.
      Supplemental Figure 2: ABIN-1 restriction of proinflammatory MyD88 signals.
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The Journal of Immunology: 191 (2)
The Journal of Immunology
Vol. 191, Issue 2
15 Jul 2013
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Cutting Edge: ABIN-1 Protects against Psoriasis by Restricting MyD88 Signals in Dendritic Cells
Joseph A. Callahan, Gianna E. Hammer, Alexander Agelides, Bao H. Duong, Shigeru Oshima, Jeffrey North, Rommel Advincula, Nataliya Shifrin, Hong-An Truong, Jonathan Paw, Julio Barrera, Anthony DeFranco, Michael D. Rosenblum, Barbara A. Malynn, Averil Ma
The Journal of Immunology July 15, 2013, 191 (2) 535-539; DOI: 10.4049/jimmunol.1203335

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Cutting Edge: ABIN-1 Protects against Psoriasis by Restricting MyD88 Signals in Dendritic Cells
Joseph A. Callahan, Gianna E. Hammer, Alexander Agelides, Bao H. Duong, Shigeru Oshima, Jeffrey North, Rommel Advincula, Nataliya Shifrin, Hong-An Truong, Jonathan Paw, Julio Barrera, Anthony DeFranco, Michael D. Rosenblum, Barbara A. Malynn, Averil Ma
The Journal of Immunology July 15, 2013, 191 (2) 535-539; DOI: 10.4049/jimmunol.1203335
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