Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions

Niess, Jan Hendrik; Leithäuser, Frank; Adler, Guido; Reimann, Jörg

doi:10.4049/jimmunol.180.1.559

Cited by 169 publications

(137 citation statements)

References 59 publications

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“…In this regard, the numbers of IL-17A producing TH17 cells is reduced in the lamina propria of GF animals [70] . Because commensal flora is a major driving force of the homeostatic proliferation of naïve T cells in the periphery, the reduced cellularity in the immune system of GF mice may be the result of the deficient peripheral expansion of recent thymic T cell emigrants [71,72] .…”

Section: Immune Responses To the Commensal Floramentioning

confidence: 96%

“…Studies in which TH1 and TH17 cells were generated co-cultures, in which naïve T cells were cultured with fecal extracts pulsed DCs, and in the presence of TH1 or TH17 promoting cytokines indicated that TH17 cells are more pathogenic than TH1 cells [118] . Recent published observations report that colitis induced by transfer of IFNγ-deficient T cells in RAG -/-mice is associated with elevated numbers of TH17 cells in the lamina propria [70] . The adoptive transfer of IL-17F, but not IL-17A deficient CD4 T cells ameliorated the IBD in the transfer model [119,120] .…”

Section: Dcs In Ibdmentioning

confidence: 99%

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Role of mucosal dendritic cells in inflammatory bowel disease

Niess

2008

WJG

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The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigenrich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

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Section: Immune Responses To the Commensal Floramentioning

confidence: 96%

Section: Dcs In Ibdmentioning

confidence: 99%

Role of mucosal dendritic cells in inflammatory bowel disease

Niess

2008

WJG

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“…Th17 cells may also contribute to the pathogenesis of enterocolitis in IL-10-deficient mice (56). IL-23 induces the differentiation of naive CD4 ϩ T cells into Th17 cells (57).…”

Section: Discussionmentioning

confidence: 99%

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Sasaki¹,

Suzuki

Kent

et al. 2008

The Journal of Immunology

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Periodontal disease is a chronic inflammatory disease in the oral cavity, which culminates in alveolar bone loss. Porphyromonas gingivalis is a consensus periodontal pathogen that has been implicated in adult forms of periodontitis. We previously demonstrated that IL-10-deficient mice exhibit a hyperinflammatory phenotype and are highly susceptible to P. gingivalis-induced periodontitis, indicating an important anti-inflammatory effect of IL-10 in suppressing bone loss. In this study, we analyzed the pathway(s) by which IL-10 deficiency leads to severe P. gingivalis-induced periodontitis. Because Stat3 is essential in IL-10 signaling, immune cell-specific Stat3-deficient mice were subjected to P. gingivalis infection to identify the key IL-10-responsive cells in preventing periodontitis. Myeloid cell-specific Stat3-deficient mice exhibited increased periodontal bone loss (p < 0.001), whereas T cell- and B cell-specific Stat3 mice were resistant, suggesting that macrophages (MP) and/or polymorphonuclear leukocytes are the key target cells normally suppressed by IL-10. Myeloid cell-specific Stat3-deficient mice exhibited elevated gingival CD40L gene expression in vivo compared with wild-type controls (p < 0.01), and Stat3-deficient MPs exhibited vigorous P. gingivalis-stimulated IL-12 production in vitro and induced elevated Ag-specific T cell proliferation compared with wild-type MPs (p < 0.01). Of importance, both IL-12p40/IL-10 and T cell/IL-10 double-deficient mice were resistant to P. gingivalis-induced periodontitis, demonstrating roles for both IL-12p40 and T cells in pathogenesis in a hyperinflammatory model of disease. These data demonstrate that P. gingivalis-induced periodontitis in IL-10-deficient mice is dependent upon IL-12p40-mediated proinflammatory T cell responses.

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“…segmented filamentous bacteria, have been reported to induce this IL-17-secreting CD4 + T-cell subset. [28][29][30] Interleukin-23 has also been reported to inhibit the accumulation of intestinal Foxp3 + regulatory T (Treg) cells, a population of CD4 + T cells of importance for maintaining intestinal homeostasis. 31 Hence, using the Tcell transfer model of colitis, in which disease is induced in T-cell-deficient Rag (Fig.…”

Section: Interleukin-23 Has Broad Effects On Both T Cells and Non-t Cmentioning

confidence: 99%

Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

2011

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Summary Interleukin‐23 (IL‐23) plays an essential role in driving intestinal pathology in experimental models of both T‐cell‐dependent and innate colitis. Furthermore, genome‐wide association studies have identified several single‐nucleotide polymorphisms in the IL‐23 receptor (IL‐23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4+ T helper 17 (Th17) cells, IL‐23 is now recognized as having multiple effects on the immune response, including restraining Foxp3+ regulatory T‐cell activity and inducing the expression of Th17‐type cytokines from non‐T‐cell sources. Here we focus on Th17 cells and their associated cytokines IL‐17A, IL‐17F, IL‐21 and IL‐22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue‐protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL‐17 expression and turn on interferon‐γ production to become Th1‐like ‘ex‐Th17’ cells. Interleukin‐23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL‐23 promotes pathology in the intestinal tract. These ‘ex‐Th17’ cells may contribute to disease pathogenesis through their secretion of pro‐inflammatory mediators.

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Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions

Cited by 169 publications

References 59 publications

Role of mucosal dendritic cells in inflammatory bowel disease

Role of mucosal dendritic cells in inflammatory bowel disease

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

Interleukin-23 and T helper 17-type responses in intestinal inflammation: from cytokines to T-cell plasticity

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