T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

被引：463

作者：

Biton, Moshe ^{[1
,2
,3
]}

Haber, Adam L. ^{[1
,2
]}

Rogel, Noga ^{[1
,2
]}

Burgin, Grace ^{[1
,2
]}

Beyaz, Semir ^{[4
,5
,6
,7
]}

Schnell, Alexandra ^{[8
]}

Ashenberg, Orr ^{[1
,2
]}

Su, Chien-Wen ^{[9
,10
]}

Smillie, Christopher ^{[1
,2
]}

Shekhar, Karthik ^{[1
,2
]}

Chen, Zuojia ^{[8
]}

Wu, Chuan ^{[8
]}

Ordovas-Montanes, Jose ^{[11
,12
,13
,14
,15
,16
]}

Alvarez, David ^{[17
,18
]}

Herbst, Rebecca H. ^{[1
,2
,19
]}

Zhang, Mei ^{[9
,10
]}

Tirosh, Itay ^{[1
,2
,20
]}

Dionne, Danielle ^{[1
,2
]}

Nguyen, Lan T. ^{[1
,2
]}

Xifaras, Michael E. ^{[4
]}

Shalek, Alex K. ^{[11
,12
,13
,14
,15
,16
]}

von Andrian, Ulrich H.

Graham, Daniel B. ^{[13
,14
]}

Rozenblatt-Rosen, Orit ^{[1
,2
]}

Shi, Hai Ning ^{[9
,10
]}

Kuchroo, Vijay ^{[8
,13
,14
]}

Yilmaz, Omer H. ^{[4
,13
,14
,21
]}

Regev, Aviv ^{[1
,2
,4
,22
]}

Xavier, Ramnik J. ^{[3
,13
,14
,23
,24
,25
]}

机构：

[1] Broad Inst Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA

[2] MIT, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] MIT, Dept Biol, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[5] Harvard Med Sch, Boston Childrens Hosp, Divis Hematol Oncol, Boston, MA 02115 USA

[6] Harvard Med Sch, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[8] Harvard Med Sch, Brigham & Womens Hosp, Evergrande Ctr Immunol Dis, Boston, MA USA

[9] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA

[10] Harvard Med Sch, Charlestown, MA 02129 USA

[11] MIT, IMES, Cambridge, MA 02139 USA

[12] MIT, Dept Chem, Cambridge, MA 02139 USA

[13] Broad Inst Harvard, Cambridge, MA 02142 USA

[14] MIT, Cambridge, MA 02142 USA

[15] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA

[16] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA

[17] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[18] Harvard Med Sch, Ctr Immune Imaging, Boston, MA 02115 USA

[19] Harvard Med Sch, Dept Syst Biol, Boston, MA 02114 USA

[20] Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel

[21] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[22] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA

[23] MIT, Gastrointestinal Unit, Boston, MA 02114 USA

[24] MIT, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[25] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA

来源：

CELL | 2018年 / 175卷 / 05期

关键词：

RNA-SEQ; MUCOSAL IMMUNITY; EPITHELIAL-CELLS; EXPRESSION; SPECIFICITY; CRYPT; MAPS; MICE;

D O I：

10.1016/j.cell.2018.10.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells it the niche affect ISC fate or the balance between self-rei and differentiation. Here, we use single cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr(5+) ISCs. We show that MHCII+ Lgr(5+) ISCs are non-conventional antigen-presenting cells in co-cultures with CD4( +) T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr(5+) ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr(5+) ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr(5+) ISCs, thus, orchestrate, tissue-wide responses to external signals.

引用

页码：1307 / +

页数：36

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