Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells

Iliev, Iliyan D.; Spadoni, Ilaria; Mileti, Erika; Matteoli, Gianluca; Sonzogni, Angelica; Sampietro, Gianluca; Foschi, Diego; Caprioli, Flavio; Viale, Giuseppe; Rescigno, María

doi:10.1136/gut.2008.175166

Cited by 337 publications

(324 citation statements)

References 34 publications

(76 reference statements)

Supporting

Mentioning

292

Contrasting

Unclassified

Order By: Relevance

“…Intestinal macrophages are also reported to induce Foxp3 + T reg cells (22) a property to induce T reg cells (39,40). CX 3 CR1 high M reg cells localize very close to intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Kayama

Ueda

Sawa

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Adequate activation of CD4 + T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4 + T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX 3 C chemokine receptor 1 high (CX 3 CR1 high ) CD11b + CD11c + cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4 + T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX 3 CR1 high CD11b + CD11c + cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX 3 CR1 high CD11b + CD11c + cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis. mucosal immunology | innate immunity

show abstract

Section: Discussionmentioning

confidence: 99%

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Kayama

Ueda

Sawa

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Thus, tolerogenic "gutlike" DCs can be generated when they are exposed to such microenvironments [22][23][24][25][26]. In UC patients, immune homeostasis in the gastrointestinal tract is compromised.…”

Section: Introductionmentioning

confidence: 99%

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

et al. 2012

View full text Add to dashboard Cite

Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.Keywords: Dendritic cells r IL-6 r Mucosal immunity r Intestinal immunity r Ulcerative colitis Correspondence: Prof. Stella C. Knight e-mail: s.knight@imperial.ac.uk IntroductionThe gastrointestinal tract is in contact with a wide variety of commensal microbiota and diverse pathogens, and therefore C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 1338 David Bernardo et al. Eur. J. Immunol. 2012. 42: 1337-1353 requires a balance to be maintained between immunity and immune tolerance; the lack of immune responses against food antigens and/or the commensal microbiota is essential to maintain the homeostasis of the gastrointestinal tract [1]. Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), traditionally related to a Th2 cytokine profile mediated by 3], where immune homeostasis of the gastrointestinal tract is compromised. Up to 1/3rd of UC patients can develop extraintestinal manifestations with the skin being one of such tissues [4,5].Dendritic cells (DCs) are the most potent antigen presenting cells and determine the nature and type of immune responses [6,7]. Intestinal DCs control immune tolerance in the gastrointestinal tract [8][9][10]. DCs also maintain immune responses localized to specific tissues, since they imprint specific tissue-homing profiles on stimulated T cells [11]. Retinoic acid (RA), the active form of vitamin A following dehydrogenization by the RALDH2 enzyme controls some of the mechanisms of immune homeostasis of the gut [12][13][14]. RA-producing DCs mediate the IgA switching of B cells [15], the generation of T cells with a regulatory phenotype [10], and the imprinting of gut-homing markers on B and T cells [16,17], thereby keeping tolerogenic immune responses com...

show abstract

“…Different DC subsets in human MLNs have recently been described and are summarized in Table 2. In two different studies, the presence of CD103 + and CD103 -DC subsets in MLNs has been reported [20,45]. The CD103 + population had a higher expression of CD40, CD83 and CCR7 compared to the CD103 -population and probably represents an activated lamina propria-derived migratory DC population [45].…”

Section: Subsets In Human Mesenteric Lymph Nodesmentioning

confidence: 98%

“…In two different studies, the presence of CD103 + and CD103 -DC subsets in MLNs has been reported [20,45]. The CD103 + population had a higher expression of CD40, CD83 and CCR7 compared to the CD103 -population and probably represents an activated lamina propria-derived migratory DC population [45]. In addition, allogeneic mixed lymphocyte reactions between CD103 + DCs and naïve CD4 + T cells induced FoxP3 + T reg cells with a reduction of IFN-γ production [45] as well as induced expression of the gut homing receptors CCR9 and α4β7 on the CD4 + T cells [20].…”

Section: Subsets In Human Mesenteric Lymph Nodesmentioning

confidence: 99%

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Magnusson

Wick

2011

European Journal of Microbiology and Immunology

View full text Add to dashboard Cite

Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells

Abstract: A population of tolerogenic CD103+ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive T(reg) cell development.

Cited by 337 publications

References 34 publications

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Contact Info

Product

Resources

About

Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells

Abstract: A population of tolerogenic CD103+ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive T(reg) cell development.

Cited by 337 publications

References 34 publications

Intestinal CX 3 C chemokine receptor 1 high (CX 3 CR1 high ) myeloid cells prevent T-cell-dependent colitis

Intestinal CX 3 C chemokine receptor 1 high (CX 3 CR1 high ) myeloid cells prevent T-cell-dependent colitis

IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and Tcells they stimulate

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Contact Info

Product

Resources

About

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis