Intestinal CD103(+)CD11b(-) Dendritic Cells Restrain Colitis Via IFN-γ-induced Anti-inflammatory Response in Epithelial Cells

Overview

Journal Mucosal Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2015 Jul 16

PMID 26174764

Citations 72

Authors

A R B M Muzaki

P Tetlak

J Sheng

S C Loh

Y A Setiagani

M Poidinger

F Zolezzi

K Karjalainen

C Ruedl

Affiliations

Soon will be listed here.

Abstract

A crosstalk between commensals, gut immune cells, and colonic epithelia is required for a proper function of intestinal mucosal barrier. Here we investigated the importance of two distinct intestinal dendritic cell (DC) subsets in controlling intestinal inflammation. We show that Clec9A-diphtheria toxin receptor (DTR) mice after depletion of CD103(+)CD11b(-) DCs developed severe, low-dose dextran sodium sulfate (DSS)-induced colitis, whereas the lack of CD103(+)CD11b(+) DCs in Clec4a4-DTR mice did not exacerbate intestinal inflammation. The CD103(+)CD11b(-) DC subset has gained a functional specialization that able them to repress inflammation via several epithelial interferon-γ (IFN-γ)-induced proteins. Among others, we identified that epithelial IDO1 and interleukin-18-binding protein (IL-18bp) were strongly modulated by CD103(+)CD11b(-) DCs. Through its preferential property to express IL-12 and IL-15, this particular DC subset can induce lymphocytes in colonic lamina propria and in epithelia to secrete IFN-γ that then can trigger a reversible early anti-inflammatory response in intestinal epithelial cells.

Citing Articles

Origin, Function, and Implications of Intestinal and Hepatic Macrophages in the Pathogenesis of Alcohol-Associated Liver Disease.

Hu Y, Schnabl B, Starkel P Cells. 2025; 14(3).

PMID: 39936998 PMC: 11816606. DOI: 10.3390/cells14030207.

Type 2 conventional dendritic cell functional heterogeneity: ontogenically committed or environmentally plastic?.

Leon B Trends Immunol. 2025; 46(2):104-120.

PMID: 39843310 PMC: 11835539. DOI: 10.1016/j.it.2024.12.005.

Dissecting Innate and Adaptive Immunity in Inflammatory Bowel Disease: Immune Compartmentalization, Microbiota Crosstalk, and Emerging Therapies.

Yue N, Hu P, Tian C, Kong C, Zhao H, Zhang Y J Inflamm Res. 2024; 17:9987-10014.

PMID: 39634289 PMC: 11615095. DOI: 10.2147/JIR.S492079.

Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis.

Cai Y, Li S, Yang Y, Duan S, Fan G, Bai J Theranostics. 2024; 14(11):4393-4410.

PMID: 39113810 PMC: 11303083. DOI: 10.7150/thno.96184.

A novel model of the small intestinal epithelium in co-culture with 'gut-like' dendritic cells.

Johnston L, Barningham L, Campbell E, Cerovic V, Duckworth C, Luu L Discov Immunol. 2024; 2(1):kyad018.

PMID: 38567056 PMC: 10917230. DOI: 10.1093/discim/kyad018.

References

Farache J, Koren I, Milo I, Gurevich I, Kim K, Zigmond E . Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. Immunity. 2013; 38(3):581-95. PMC: 4115273. DOI: 10.1016/j.immuni.2013.01.009. View

Schulz O, Jaensson E, Persson E, Liu X, Worbs T, Agace W . Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med. 2009; 206(13):3101-14. PMC: 2806467. DOI: 10.1084/jem.20091925. View

Peeters M, Geypens B, Claus D, Nevens H, Ghoos Y, Verbeke G . Clustering of increased small intestinal permeability in families with Crohn's disease. Gastroenterology. 1997; 113(3):802-7. DOI: 10.1016/s0016-5085(97)70174-4. View

Fuchs A, Vermi W, Lee J, Lonardi S, Gilfillan S, Newberry R . Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells. Immunity. 2013; 38(4):769-81. PMC: 3634355. DOI: 10.1016/j.immuni.2013.02.010. View

Farache J, Zigmond E, Shakhar G, Jung S . Contributions of dendritic cells and macrophages to intestinal homeostasis and immune defense. Immunol Cell Biol. 2013; 91(3):232-9. DOI: 10.1038/icb.2012.79. View

Berndt B, Zhang M, Chen G, Huffnagle G, Kao J . The role of dendritic cells in the development of acute dextran sulfate sodium colitis. J Immunol. 2007; 179(9):6255-62. DOI: 10.4049/jimmunol.179.9.6255. View

Dalton D, Keshav S, Figari I, Bradley A, Stewart T . Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993; 259(5102):1739-42. DOI: 10.1126/science.8456300. View

Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy A, Friedlander G . Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012; 37(6):1076-90. DOI: 10.1016/j.immuni.2012.08.026. View

Thelemann C, Eren R, Coutaz M, Brasseit J, Bouzourene H, Rosa M . Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis. PLoS One. 2014; 9(1):e86844. PMC: 3904943. DOI: 10.1371/journal.pone.0086844. View

10.

Hurgin V, Novick D, Rubinstein M . The promoter of IL-18 binding protein: activation by an IFN-gamma -induced complex of IFN regulatory factor 1 and CCAAT/enhancer binding protein beta. Proc Natl Acad Sci U S A. 2002; 99(26):16957-62. PMC: 139251. DOI: 10.1073/pnas.262663399. View

11.

Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M . Origin of the lamina propria dendritic cell network. Immunity. 2009; 31(3):513-25. PMC: 2778256. DOI: 10.1016/j.immuni.2009.08.010. View

12.

Hashimoto D, Miller J, Merad M . Dendritic cell and macrophage heterogeneity in vivo. Immunity. 2011; 35(3):323-35. PMC: 4520532. DOI: 10.1016/j.immuni.2011.09.007. View

13.

Piva L, Tetlak P, Claser C, Karjalainen K, Renia L, Ruedl C . Cutting edge: Clec9A+ dendritic cells mediate the development of experimental cerebral malaria. J Immunol. 2012; 189(3):1128-32. DOI: 10.4049/jimmunol.1201171. View

14.

Schmidt S, Schultze J . New Insights into IDO Biology in Bacterial and Viral Infections. Front Immunol. 2014; 5:384. PMC: 4128074. DOI: 10.3389/fimmu.2014.00384. View

15.

Medina-Contreras O, Geem D, Laur O, Williams I, Lira S, Nusrat A . CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. J Clin Invest. 2011; 121(12):4787-95. PMC: 3226003. DOI: 10.1172/JCI59150. View

16.

Siegmund B, Fantuzzi G, Rieder F, Gamboni-Robertson F, Lehr H, Hartmann G . Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production. Am J Physiol Regul Integr Comp Physiol. 2001; 281(4):R1264-73. DOI: 10.1152/ajpregu.2001.281.4.R1264. View

17.

Ito R, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J . Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clin Exp Immunol. 2006; 146(2):330-8. PMC: 1942055. DOI: 10.1111/j.1365-2249.2006.03214.x. View

18.

Peterson L, Artis D . Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014; 14(3):141-53. DOI: 10.1038/nri3608. View

19.

Miller J, Brown B, Shay T, Gautier E, Jojic V, Cohain A . Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012; 13(9):888-99. PMC: 3985403. DOI: 10.1038/ni.2370. View

20.

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