Interleukin 6 Increases Production of Cytokines by Colonic Innate Lymphoid Cells in Mice and Patients With Chronic Intestinal Inflammation

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus–triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell–specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4+ T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4+ T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.

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Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147618 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7618

Author(s):

Angela Saez ◽

Raquel Gomez-Bris ◽

Beatriz Herrero-Fernandez ◽

Claudia Mingorance ◽

Cristina Rius ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Intestinal Homeostasis ◽

Mucosal Homeostasis ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.

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Faculty Opinions recommendation of IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717955912.793460834 ◽

2012 ◽

Author(s):

Anne Mueller

Keyword(s):

Th17 Cells ◽

Intestinal Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Chronic Intestinal Inflammation

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Faculty Opinions recommendation of Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717951515.793456819 ◽

2012 ◽

Author(s):

Xian C Li

Keyword(s):

Intestinal Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Inflammatory Monocytes ◽

Interleukin 15

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Innate Lymphoid Cells in Intestinal Inflammation

Frontiers in Immunology ◽

10.3389/fimmu.2017.01296 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 55

Author(s):

Alessandra Geremia ◽

Carolina V. Arancibia-Cárcamo

Keyword(s):

Intestinal Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells

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Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo

Nature Medicine ◽

10.1038/75068 ◽

2000 ◽

Vol 6 (5) ◽

pp. 583-588 ◽

Cited By ~ 841

Author(s):

R. Atreya ◽

J. Mudter ◽

S. Finotto ◽

J. Müllberg ◽

T. Jostock ◽

...

Keyword(s):

T Cell ◽

Crohn Disease ◽

Interleukin 6 ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Cell Resistance ◽

Chronic Intestinal Inflammation

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Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis

10.21203/rs.3.rs-731878/v1 ◽

2021 ◽

Author(s):

Jiří Hrdý ◽

Aurélie Couturier-Maillard ◽

Denise Boutillier ◽

Carmen Lapadatescu ◽

Philippe Blanc ◽

...

Keyword(s):

Inflammatory Bowel Diseases ◽

Lactobacillus Acidophilus ◽

Target Genes ◽

Intestinal Inflammation ◽

Probiotic Strain ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Trinitrobenzene Sulfonic Acid ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.

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