CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis

被引:44
|
作者
Matsuno, Hiroshi [1 ]
Kayama, Hisako [2 ,3 ,4 ]
Nishimura, Junichi [1 ]
Sekido, Yuki [1 ]
Osawa, Hideki [1 ]
Barman, Soumik [2 ]
Ogino, Takayuki [1 ]
Takahashi, Hidekazu [1 ]
Haraguchi, Naotsugu [1 ]
Hata, Taishi [1 ]
Matsuda, Chu [1 ]
Yamamoto, Hirofumi [1 ,5 ]
Uchino, Motoi [6 ]
Ikeuchi, Hiroki [6 ]
Doki, Yuichiro [1 ]
Mori, Masaki [1 ]
Takeda, Kiyoshi [2 ,3 ,4 ]
Mizushima, Tsunekazu [1 ,7 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Immune Regulat, Suita, Osaka, Japan
[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Mucosal Immunol, Suita, Osaka, Japan
[4] Japan Agcy Med Res & Dev, Core Res Evolut Sci & Technol, Chiyoda Ku, Tokyo, Japan
[5] Osaka Univ, Grad Sch Med & Hlth Sci, Div Hlth Sci, Dept Mol Pathol, Suita, Osaka, Japan
[6] Hyogo Coll Med, Dept Inflammatory Bowel Dis, Nishinomiya, Hyogo, Japan
[7] Osaka Univ, Grad Sch Med, Dept Therapeut Inflammatory Bowel Dis, Suita, Osaka, Japan
关键词
ulcerative colitis; human large intestinal lamina propria; CD103(+) dendritic cell; Foxp3(+) regulatory T cells; INTESTINAL LAMINA PROPRIA; REGULATORY T-CELLS; CROHNS-DISEASE; RETINOIC-ACID; GUT HOMEOSTASIS; MACROPHAGES; RESPONSES; IMMUNITY; SUBSET; INTERLEUKIN-13;
D O I
10.1097/MIB.0000000000001204
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DR(high)CD14(+) cells, HLA-DR(high)CD103(+) dendritic cells (DCs), and HLA-DR(high)CD14(-)CD103(-) cells. CD103(+) DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103(+) DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). Methods: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24). Noninflamed and inflamed colonic tissues were obtained from surgically resected specimens of patients with UC (n = 13). Among Lin(-)CD45(+) HLA-DRhigh intestinal lamina propria cells, CD14(+) cells and CD103(+) DCs were sorted and analyzed for microRNA expression of cytokines and toll-like receptors by quantitative real-time polymerase chain reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-gamma production and Foxp3 expression by naive T cells cultured with CD14(+) cells and CD103(+) DCs were analyzed. Results: CD103(+) DCs in the normal colon showed lower expression of toll-like receptors and proinflammatory cytokines than CD14(+) cells. Coculture with naive T cells revealed that CD103(+) DCs generated Treg cells. CD103+ DCs from patients with UC did not generate Treg cells, but they induced IFN-gamma-, IL-13-, and IL-17-producing CD4(+) T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P < 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05). Conclusions: In patients with UC, CD103(+) DCs show the impaired ability to generate Treg cells, but exhibit a colitogenic function inducing Th1/Th2/Th17 responses. These findings show how human CD103(+) DCs could contribute to the pathogenesis of UC.
引用
收藏
页码:1524 / 1534
页数:11
相关论文
共 50 条
  • [1] CD103+ Dendritic Cells Control Th17 Cell Function in the Lung
    Zelante, Teresa
    Wong, Alicia Yoke Wei
    Ping, Tang Jing
    Chen, Jinmiao
    Sumatoh, Hermi R.
    Vigano, Elena
    Bing, Yu Hong
    Lee, Bernett
    Zolezzi, Francesca
    Fric, Jan
    Newell, Evan W.
    Mortellaro, Alessandra
    Poidinger, Michael
    Puccetti, Paolo
    Ricciardi-Castagnoli, Paola
    CELL REPORTS, 2015, 12 (11): : 1789 - 1801
  • [2] TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer
    Pulido, Alvaro de Mingo
    Gardner, Alycia
    Hiebler, Shandi
    Soliman, Hatem
    Rugo, Hope S.
    Krummel, Matthew F.
    Coussens, Lisa M.
    Ruffell, Brian
    CANCER CELL, 2018, 33 (01) : 60 - +
  • [3] A Local Role for CD103+ Dendritic Cells in Atherosclerosis
    Bedoui, Sammy
    Heath, William R.
    IMMUNITY, 2011, 35 (05) : 665 - 667
  • [4] CD103+ intestinal dendritic cells - location and regulation
    Johnson, A.
    Powrie, F.
    IMMUNOLOGY, 2010, 131 : 83 - 83
  • [5] Blood monocyte subsets differentially give rise to CD103+ and CD103- pulmonary dendritic cell populations
    Jakubzick, Claudia
    Tacke, Frank
    Ginhoux, Florent
    Wagers, Amy J.
    van Rooijen, Nico
    Mack, Matthias
    Merad, Miriam
    Randolph, Gwendalyn J.
    JOURNAL OF IMMUNOLOGY, 2008, 180 (05): : 3019 - 3027
  • [6] Intestinal CD103+ dendritic cells: master regulators of tolerance?
    Scott, Charlotte L.
    Aumeunier, Aude M.
    Mowat, Allan Mcl.
    TRENDS IN IMMUNOLOGY, 2011, 32 (09) : 412 - 419
  • [7] CD55 Is Essential for CD103+ Dendritic Cell Tolerogenic Responses that Protect against Autoimmunity
    Strainic, Michael G.
    Liu, Jinbo
    An, Fengqi
    Bailey, Erin
    Esposito, Andrew
    Hamann, Jorg
    Heeger, Peter S.
    Medof, M. Edward
    AMERICAN JOURNAL OF PATHOLOGY, 2019, 189 (07): : 1386 - 1401
  • [8] Dysregulated gut homing in patients with ulcerative colitis is associated with altered CD103 (alpha-E) expression by human colonic dendritic cells
    Ng, S. C.
    Plamondon, S.
    Kamm, M. A.
    Knight, S. C.
    Stagg, A. J.
    IMMUNOLOGY, 2008, 125 : 23 - 23
  • [9] How to generate large numbers of CD103+ dendritic cells
    van de Laar, Lianne
    Lambrecht, Bart N.
    BLOOD, 2014, 124 (20) : 3036 - 3038
  • [10] Integrin αvβ8 Promotes Tolerogenic Function of CD103+ Dendritic Cells in Corneal Transplantation
    Blanco, Tomas
    Atilla, Serra
    Dana, Reza
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2019, 60 (09)