Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation

被引：49

作者：

Capucha, Tal ^{[1
]}

Koren, Noam ^{[1
]}

Nassar, Maria ^{[1
]}

Heyman, Oded ^{[2
]}

Nir, Tsipora ^{[1
]}

Levy, Maayan ^{[3
]}

Zilberman-Schapira, Gili ^{[3
]}

Zelentova, Katya ^{[1
]}

Eli-Berchoer, Luba ^{[1
]}

Zenke, Martin ^{[4
,5
]}

Hieronymus, Thomas ^{[4
,5
]}

Wilensky, Asaf ^{[2
]}

Bercovier, Herve ^{[6
]}

Elinav, Eran ^{[3
]}

Clausen, Bjoern E. ^{[7
]}

Hovav, Avi-Hai ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Med Ctr, Fac Dent Med, Inst Dent Sci, Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Hadassah Med Ctr, Fac Dent Med, Dept Periodontol, Jerusalem, Israel

[3] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[4] Rhein Westfal TH Aachen, Med Fac, Dept Cell Biol, Inst Biomed Engn, Aachen, Germany

[5] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, Aachen, Germany

[6] Hebrew Univ Jerusalem, Dept Microbiol & Mol Genet, Fac Med, Jerusalem, Israel

[7] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2018年 / 215卷 / 02期

基金：

以色列科学基金会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; BONE MORPHOGENETIC PROTEIN-7; DENDRITIC CELLS; STEADY-STATE; TGF-BETA; T-CELLS; SKIN; DISTINCT; INFLAMMATION; REGULATORS;

D O I：

10.1084/jem.20171508

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-beta 1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-beta 1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

引用

页码：481 / 500

页数：20

共 57 条

[1] Langerhans cells down-regulate inflammation-driven alveolar bone loss [J].

Arizon, Moran ;

Nudel, Itay ;

Segev, Hadas ;

Mizraji, Gabriel ;

Elnekave, Mazal ;

Furmanov, Karina ;

Eli-Berchoer, Luba ;

Clausen, Bjorn E. ;

Shapira, Lior ;

Wilensky, Asaf ;

Hovav, Avi-Hai .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (18) :7043-7048

[2] TGFβ/TNFα-Mediated Epithelial-Mesenchymal Transition Generates Breast Cancer Stem Cells with a Claudin-Low Phenotype [J].

Asiedu, Michael K. ;

Ingle, James N. ;

Behrens, Marshall D. ;

Radisky, Derek C. ;

Knutson, Keith L. .

CANCER RESEARCH, 2011, 71 (13) :4707-4719

[3] Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice [J].

Bain, Calum C. ;

Bravo-Blas, Alberto ;

Scott, Charlotte L. ;

Perdiguero, Elisa Gomez ;

Geissmann, Frederic ;

Henri, Sandrine ;

Malissen, Bernard ;

Osborne, Lisa C. ;

Artis, David ;

Mowat, Allan Mci .

NATURE IMMUNOLOGY, 2014, 15 (10) :929-U236

[4] Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis [J].

Bauer, Thomas ;

Zagorska, Anna ;

Jurkin, Jennifer ;

Yasmin, Nighat ;

Koeffel, Rene ;

Richter, Susanne ;

Gesslbauer, Bernhard ;

Lemke, Greg ;

Strobl, Herbert .

JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (11) :2033-2047

[5] Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity [J].

Bennett, CL ;

van Rijn, E ;

Jung, S ;

Inaba, K ;

Steinman, RM ;

Kapsenberg, ML ;

Clausen, BE .

JOURNAL OF CELL BIOLOGY, 2005, 169 (04) :569-576

[6] DC ablation in mice: promises, pitfalls, and challenges [J].

Bennett, Clare L. ;

Clausen, Bjoern E. .

TRENDS IN IMMUNOLOGY, 2007, 28 (12) :525-531

[7] Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells [J].

Bigley, Venetia ;

McGovern, Naomi ;

Milne, Paul ;

Dickinson, Rachel ;

Pagan, Sarah ;

Cookson, Sharon ;

Haniffa, Muzlifah ;

Collin, Matthew .

JOURNAL OF LEUKOCYTE BIOLOGY, 2015, 97 (04) :627-634

[8] Mucosal Langerhans Cells Promote Differentiation of Th17 Cells in a Murine Model of Periodontitis but Are Not Required for Porphyromonas gingivalis-Driven Alveolar Bone Destruction [J].

Bittner-Eddy, Peter D. ;

Fischer, Lori A. ;

Kaplan, Daniel H. ;

Thieu, Kathleen ;

Costalonga, Massimo .

JOURNAL OF IMMUNOLOGY, 2016, 197 (04) :1435-1446

[9] Acute Ablation of Langerhans Cells Enhances Skin Immune Responses [J].

Bobr, Aleh ;

Olvera-Gomez, Irlanda ;

Igyarto, Botond Z. ;

Haley, Krystal M. ;

Hogquist, Kristin A. ;

Kaplan, Daniel H. .

JOURNAL OF IMMUNOLOGY, 2010, 185 (08) :4724-4728

[10] A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: The skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells [J].

Borkowski, TA ;

Letterio, JJ ;

Farr, AG ;

Udey, MC .

JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (06) :2417-2422

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