Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals

被引：602

作者：

Shan, Meimei ^{[1
]}

Gentile, Maurizio ^{[2
]}

Yeiser, John R. ^{[1
]}

Walland, A. Cooper ^{[1
]}

Bornstein, Victor U. ^{[1
]}

Chen, Kang ^{[1
,3
]}

He, Bing ^{[1
]}

Cassis, Linda ^{[2
]}

Bigas, Anna ^{[4
]}

Cols, Montserrat ^{[1
]}

Comerma, Laura ^{[2
,5
]}

Huang, Bihui ^{[6
]}

Blander, J. Magarian ^{[1
,7
]}

Xiong, Huabao ^{[1
]}

Mayer, Lloyd ^{[1
]}

Berin, Cecilia ^{[8
]}

Augenlicht, Leonard H. ^{[9
]}

Velcich, Anna ^{[9
]}

Cerutti, Andrea ^{[1
,2
,10
,11
]}

机构：

[1] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY USA

[2] Inst Hosp Mar Invest Med IMIM, Program Inflammatory & Cardiovasc Disorders, Barcelona, Spain

[3] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA

[4] IMIM, Program Canc Res, Barcelona, Spain

[5] Hosp del Mar, Dept Pathol, Barcelona, Spain

[6] Yale Univ, Dept Pharmacol, New Haven, CT USA

[7] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA

[8] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Pediat, New York, NY USA

[9] Albert Einstein Coll Med, Dept Med, New York, NY USA

[10] NIH, Mucosal Immunol Studies Team MIST, Bethesda, MD 20892 USA

[11] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain

来源：

SCIENCE | 2013年 / 342卷 / 6157期

关键词：

CD103(+) DENDRITIC CELLS; T-CELLS; EPITHELIAL-CELLS; BETA-CATENIN; DECTIN-1; DIFFERENTIATION; ASSOCIATION; IMMUNITY; ANTIGEN; MUCIN;

D O I：

10.1126/science.1237910

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-Fc gamma RIIB receptor complex that activated beta-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor kappa B. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals.

引用

页码：447 / 453

页数：7

共 28 条

[1]

Origin of the Lamina Propria Dendritic Cell Network [J].

Bogunovic, Milena ;

Ginhoux, Florent ;

Helft, Julie ;

Shang, Limin ;

Hashimoto, Daigo ;

Greter, Melanie ;

Liu, Kang ;

Jakubzick, Claudia ;

Ingersoll, Molly A. ;

Leboeuf, Marylene ;

Stanley, E. Richard ;

Nussenzweig, Michel ;

Lira, Sergio A. ;

Randolph, Gwendalyn J. ;

Merad, Miriam .

IMMUNITY, 2009, 31 (03) :513-525

[2]

Immunoglobulin Responses at the Mucosal Interface [J].

Cerutti, Andrea ;

Chen, Kang ;

Chorny, Alejo .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :273-293

[3]

Dendritic cells in intestinal immune regulation [J].

Coombes, Janine L. ;

Powrie, Fiona .

NATURE REVIEWS IMMUNOLOGY, 2008, 8 (06) :435-446

[4]

A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β- and retinoic acid-dependent mechanism [J].

Coombes, Janine L. ;

Siddiqui, Karima R. R. ;

Arancibia-Carcamo, Carolina V. ;

Hall, Jason ;

Sun, Cheng-Ming ;

Belkaid, Yasmine ;

Powrie, Fiona .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1757-1764

[5]

β-catenin interacts with and inhibits NF-κB in human colon and breast cancer [J].

Deng, JO ;

Miller, SA ;

Wang, HY ;

Xia, WY ;

Wen, Y ;

Zhou, BHP ;

Li, Y ;

Lin, SY ;

Hung, MC .

CANCER CELL, 2002, 2 (04) :323-334

[6]

Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and TLR signaling pathways [J].

Dennehy, Kevin M. ;

Willment, Janet A. ;

Williams, David L. ;

Brown, Gordon D. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2009, 39 (05) :1379-1386

[7]

Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance [J].

Dillon, S ;

Agrawal, S ;

Banerjee, K ;

Letterio, J ;

Denning, TL ;

Oswald-Richter, K ;

Kasprowicz, DJ ;

Kellar, K ;

Pare, J ;

van Dyke, T ;

Ziegler, S ;

Unutmaz, D ;

Pulendran, B .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (04) :916-928

[8]

Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages [J].

Esteban, Alexandre ;

Popp, Maximilian W. ;

Vyas, Valmik K. ;

Strijbis, Karin ;

Ploegh, Hidde L. ;

Fink, Gerald R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (34) :14270-14275

[9]

Luminal Bacteria Recruit CD103+ Dendritic Cells into the Intestinal Epithelium to Sample Bacterial Antigens for Presentation [J].

Farache, Julia ;

Koren, Idan ;

Milo, Idan ;

Gurevich, Irina ;

Kim, Ki-Wook ;

Zigmond, Ehud ;

Furtado, Glaucia C. ;

Lira, Sergio A. ;

Shakhar, Guy .

IMMUNITY, 2013, 38 (03) :581-595

[10]

Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10 [J].

Ilarregui, Juan M. ;

Croci, Diego O. ;

Bianco, German A. ;

Toscano, Marta A. ;

Salatino, Mariana ;

Vermeulen, Monica E. ;

Geffner, Jorge R. ;

Rabinovich, Gabriel A. .

NATURE IMMUNOLOGY, 2009, 10 (09) :981-U75

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