Differentiation of CD11c+ CX3CR1+ Cells in the Small Intestine Requires Notch Signaling

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2014 Apr 9

PMID 24711412

Citations 17

Authors

Chieko Ishifune

Satoshi Maruyama

Yuki Sasaki

Hideo Yagita

Katsuto Hozumi

Taisuke Tomita

Kenji Kishihara

Koji Yasutomo

Affiliations

Soon will be listed here.

Abstract

The gastrointestinal tract comes into direct contact with environmental agents, including bacteria, viruses, and foods. Intestine-specific subsets of immune cells maintain gut homeostasis by continuously sampling luminal antigens and maintaining immune tolerance. CD11c(+)CX3CR1(+) cells sample luminal antigens in the small intestine and contribute to the trafficking of bacteria to lymph nodes under dysbiotic conditions. The molecular mechanisms crucial for the differentiation of CD11c(+)CX3CR1(+) cells remain unclear. Here we demonstrate that the Notch1- or Notch2-Rbpj axis is essential for the development of CD11c(+)CX3CR1(+) cells. In mice in which Rbpj or Notch1 and Notch2 were deleted from CD11c(+) cells, there was a deficit of CD11c(+)CX3CR1(+) cells and an accumulation of CD11c(low)CX3CR1(+) cells. The CD11c(low)CX3CR1(+) cells could not differentiate to CD11c(+)CX3CR1(+) cells, suggesting that CD11c(low)CX3CR1(+) cells represent a lineage distinct from CD11c(+)CX3CR1(+) cells. These data indicate that Notch signaling is essential for lineage fixation of intestinal CD11c(+)CX3CR1(+) cells.

Citing Articles

Macrophages in intestinal homeostasis and inflammatory bowel disease.

Hegarty L, Jones G, Bain C Nat Rev Gastroenterol Hepatol. 2023; 20(8):538-553.

PMID: 37069320 DOI: 10.1038/s41575-023-00769-0.

Notch and TLR signaling coordinate monocyte cell fate and inflammation.

Gamrekelashvili J, Kapanadze T, Sablotny S, Ratiu C, Dastagir K, Lochner M Elife. 2020; 9.

PMID: 32723480 PMC: 7413669. DOI: 10.7554/eLife.57007.

The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens.

Kang L, Zhang X, Ji L, Kou T, Smith S, Zhao B J Exp Med. 2020; 217(4).

PMID: 31944217 PMC: 7144519. DOI: 10.1084/jem.20190762.

Gut macrophages: key players in intestinal immunity and tissue physiology.

Muller P, Matheis F, Mucida D Curr Opin Immunol. 2019; 62:54-61.

PMID: 31841704 PMC: 7067652. DOI: 10.1016/j.coi.2019.11.011.

Commensal microbiota drive the functional diversification of colon macrophages.

Kang B, Alvarado L, Kim T, Lehmann M, Cho H, He J Mucosal Immunol. 2019; 13(2):216-229.

PMID: 31772323 PMC: 7039809. DOI: 10.1038/s41385-019-0228-3.

References

Uematsu S, Fujimoto K, Jang M, Yang B, Jung Y, Nishiyama M . Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol. 2008; 9(7):769-76. DOI: 10.1038/ni.1622. View

Persson E, Uronen-Hansson H, Semmrich M, Rivollier A, Hagerbrand K, Marsal J . IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity. 2013; 38(5):958-69. DOI: 10.1016/j.immuni.2013.03.009. View

Fang T, Yashiro-Ohtani Y, Del Bianco C, Knoblock D, Blacklow S, Pear W . Notch directly regulates Gata3 expression during T helper 2 cell differentiation. Immunity. 2007; 27(1):100-10. PMC: 2801546. DOI: 10.1016/j.immuni.2007.04.018. View

Diehl G, Longman R, Zhang J, Breart B, Galan C, Cuesta A . Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature. 2013; 494(7435):116-20. PMC: 3711636. DOI: 10.1038/nature11809. View

Saito T, Chiba S, Ichikawa M, Kunisato A, Asai T, Shimizu K . Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity. 2003; 18(5):675-85. DOI: 10.1016/s1074-7613(03)00111-0. View

Satpathy A, Briseno C, Lee J, Ng D, Manieri N, Kc W . Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013; 14(9):937-48. PMC: 3788683. DOI: 10.1038/ni.2679. View

Caton M, Smith-Raska M, Reizis B . Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J Exp Med. 2007; 204(7):1653-64. PMC: 2118632. DOI: 10.1084/jem.20062648. View

Perez-Cabezas B, Naranjo-Gomez M, Bastos-Amador P, Requena-Fernandez G, Pujol-Borrell R, Borras F . Ligation of Notch receptors in human conventional and plasmacytoid dendritic cells differentially regulates cytokine and chemokine secretion and modulates Th cell polarization. J Immunol. 2011; 186(12):7006-15. DOI: 10.4049/jimmunol.1100203. View

Bailis W, Yashiro-Ohtani Y, Fang T, Hatton R, Weaver C, Artis D . Notch simultaneously orchestrates multiple helper T cell programs independently of cytokine signals. Immunity. 2013; 39(1):148-59. PMC: 3762693. DOI: 10.1016/j.immuni.2013.07.006. View

10.

Skarnes W, Moss J, Hurtley S, Beddington R . Capturing genes encoding membrane and secreted proteins important for mouse development. Proc Natl Acad Sci U S A. 1995; 92(14):6592-6. PMC: 41564. DOI: 10.1073/pnas.92.14.6592. View

11.

Chang S, Song J, Guleng B, Alonso Cotoner C, Arihiro S, Zhao Y . Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation. Immunity. 2012; 38(1):153-65. PMC: 3858856. DOI: 10.1016/j.immuni.2012.09.018. View

12.

Cerf-Bensussan N, Gaboriau-Routhiau V . The immune system and the gut microbiota: friends or foes?. Nat Rev Immunol. 2010; 10(10):735-44. DOI: 10.1038/nri2850. View

13.

Lewis K, Caton M, Bogunovic M, Greter M, Grajkowska L, Ng D . Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity. 2011; 35(5):780-91. PMC: 3225703. DOI: 10.1016/j.immuni.2011.08.013. View

14.

Brooker R, Hozumi K, Lewis J . Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development. 2006; 133(7):1277-86. DOI: 10.1242/dev.02284. View

15.

Radtke F, MacDonald H, Tacchini-Cottier F . Regulation of innate and adaptive immunity by Notch. Nat Rev Immunol. 2013; 13(6):427-37. DOI: 10.1038/nri3445. View

16.

Denning T, Wang Y, Patel S, Williams I, Pulendran B . Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007; 8(10):1086-94. DOI: 10.1038/ni1511. View

17.

Chieppa M, Rescigno M, Huang A, Germain R . Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med. 2006; 203(13):2841-52. PMC: 2118178. DOI: 10.1084/jem.20061884. View

18.

Xu H, Zhu J, Smith S, Foldi J, Zhao B, Chung A . Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat Immunol. 2012; 13(7):642-50. PMC: 3513378. DOI: 10.1038/ni.2304. View

19.

Hendrik Niess J, Brand S, Xiubin Gu , Landsman L, Jung S, McCormick B . CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005; 307(5707):254-8. DOI: 10.1126/science.1102901. View

20.

Hozumi K, Negishi N, Suzuki D, Abe N, Sotomaru Y, Tamaoki N . Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol. 2004; 5(6):638-44. DOI: 10.1038/ni1075. View