IL-17 Produced by Paneth Cells Drives TNF-induced Shock

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Jul 30

PMID 18663129

Citations 89

Authors

Nozomi Takahashi

Ineke Vanlaere

Riet De Rycke

Anje Cauwels

Leo A B Joosten

Erik Lubberts

Wim B van den Berg

Claude Libert

Affiliations

Soon will be listed here.

Abstract

Tumor necrosis factor (TNF) has very potent antitumor activity, but it also provokes a systemic inflammatory response syndrome that leads to shock, organ failure, and death. Here, we demonstrate that interleukin (IL)-17, a proinflammatory cytokine known to be produced mainly by activated T cells, has a critical role in this process. Antiserum against IL-17 or deletion of Il17r protected mice against a lethal TNF challenge. Serum levels of TNF-induced IL-6 and nitric oxide metabolites were significantly reduced in mice deficient in the IL-17R. TNF-induced leukocyte influx in the small intestine was reduced, and there was no injury to the small intestine. Surprisingly, electron microscopy showed that IL-17 was constitutively present in Paneth cells of the crypts. Upon TNF challenge, the intracellular pool of IL-17 in these cells was drastically reduced, suggesting rapid release of IL-17 from the granules of Paneth cells. Our findings assign a novel role for IL-17 in an acute inflammation and identify Paneth cells as a source of the IL-17 that plays a role in this process. These data indicate that innate immune cytokine responses in the local mucosa may participate in rapidly amplifying responses to systemic inflammatory challenges.

Citing Articles

Identification and Characterization of Multiple Paneth Cell Types in the Mouse Small Intestine.

Timmermans S, Wallaeys C, Garcia-Gonzalez N, Pollaris L, Saeys Y, Libert C Cells. 2024; 13(17.

PMID: 39273007 PMC: 11394207. DOI: 10.3390/cells13171435.

Gut epithelial Interleukin-17 receptor A signaling can modulate distant tumors growth through microbial regulation.

Chandra V, Li L, Le Roux O, Zhang Y, Howell R, Rupani D Cancer Cell. 2023; 42(1):85-100.e6.

PMID: 38157865 PMC: 11238637. DOI: 10.1016/j.ccell.2023.12.006.

Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model.

Chang Y, Hsing C, Chiu C, Wu Y, Hsu S, Hsu Y J Neuroinflammation. 2023; 20(1):279.

PMID: 38007487 PMC: 10676594. DOI: 10.1186/s12974-023-02952-1.

Infection and inflammation stimulate expansion of a CD74 Paneth cell subset to regulate disease progression.

Balasubramanian I, Bandyopadhyay S, Flores J, Bianchi-Smak J, Lin X, Liu H EMBO J. 2023; 42(21):e113975.

PMID: 37718683 PMC: 10620768. DOI: 10.15252/embj.2023113975.

Differentiated Epithelial Cells of the Gut.

Bonilla-Diaz A, Ordonez-Moran P Methods Mol Biol. 2023; 2650:3-16.

PMID: 37310619 DOI: 10.1007/978-1-0716-3076-1_1.

References

Lockhart E, Green A, Flynn J . IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol. 2006; 177(7):4662-9. DOI: 10.4049/jimmunol.177.7.4662. View

Jones C, Chan K . Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells. Am J Respir Cell Mol Biol. 2002; 26(6):748-53. DOI: 10.1165/ajrcmb.26.6.4757. View

Garabedian E, Roberts L, McNevin M, Gordon J . Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem. 1997; 272(38):23729-40. DOI: 10.1074/jbc.272.38.23729. View

Wilson C, Ouellette A, Satchell D, Ayabe T, Stratman J, Hultgren S . Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science. 1999; 286(5437):113-7. DOI: 10.1126/science.286.5437.113. View

Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y . Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2002; 52(1):65-70. PMC: 1773503. DOI: 10.1136/gut.52.1.65. View

Cauwels A, Van Molle W, Janssen B, Everaerdt B, Huang P, Fiers W . Protection against TNF-induced lethal shock by soluble guanylate cyclase inhibition requires functional inducible nitric oxide synthase. Immunity. 2000; 13(2):223-31. DOI: 10.1016/s1074-7613(00)00022-4. View

Bultinck J, Sips P, Vakaet L, Brouckaert P, Cauwels A . Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock. FASEB J. 2006; 20(13):2363-5. DOI: 10.1096/fj.06-5798fje. View

Keshav S, Lawson L, Chung L, Stein M, Perry V, Gordon S . Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization. J Exp Med. 1990; 171(1):327-32. PMC: 2187650. DOI: 10.1084/jem.171.1.327. View

Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls J . Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis. 2006; 12(5):382-8. DOI: 10.1097/01.MIB.0000218764.06959.91. View

10.

Libert C, Takahashi N, Cauwels A, Brouckaert P, Bluethmann H, Fiers W . Response of interleukin-6-deficient mice to tumor necrosis factor-induced metabolic changes and lethality. Eur J Immunol. 1994; 24(9):2237-42. DOI: 10.1002/eji.1830240945. View

11.

Ayabe T, Ashida T, Kohgo Y, Kono T . The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol. 2004; 12(8):394-8. DOI: 10.1016/j.tim.2004.06.007. View

12.

Park H, Li Z, Yang X, Chang S, Nurieva R, Wang Y . A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005; 6(11):1133-41. PMC: 1618871. DOI: 10.1038/ni1261. View

13.

Langrish C, Chen Y, Blumenschein W, Mattson J, Basham B, Sedgwick J . IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005; 201(2):233-40. PMC: 2212798. DOI: 10.1084/jem.20041257. View

14.

Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I . Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity. 2002; 17(3):375-87. DOI: 10.1016/s1074-7613(02)00391-6. View

15.

Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T . T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med. 2007; 204(1):41-7. PMC: 2118414. DOI: 10.1084/jem.20062259. View

16.

Weaver C, Hatton R, Mangan P, Harrington L . IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007; 25:821-52. DOI: 10.1146/annurev.immunol.25.022106.141557. View

17.

Sutton C, Brereton C, Keogh B, Mills K, Lavelle E . A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med. 2006; 203(7):1685-91. PMC: 2118338. DOI: 10.1084/jem.20060285. View

18.

Lubberts E, Koenders M, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo C, Joosten L . Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum. 2004; 50(2):650-9. DOI: 10.1002/art.20001. View

19.

Stark M, Huo Y, Burcin T, Morris M, Olson T, Ley K . Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity. 2005; 22(3):285-94. DOI: 10.1016/j.immuni.2005.01.011. View

20.

Aggarwal B, Natarajan K . Tumor necrosis factors: developments during the last decade. Eur Cytokine Netw. 1996; 7(2):93-124. View