Small intestine CD11c+CD8+T cells suppress CD4+T cell-induced immune colitis

Fujiwara, Daisuke; Chen, Ling; Wei, Bo; Braun, Jonathan

doi:10.1152/ajpgi.00032.2010

Cited by 27 publications

(31 citation statements)

References 48 publications

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“…However, CD11c + CD8 + T cells-induced and expanded by inoculation of agonistic anti-4-1 BB mAb in collagen type II-induced arthritis mice (25), experimental autoimmune uveoretinitis mice (26), and hapten-induced colitis mice (27)- were found to be regulatory T cells that suppressed Ag-specific CD4 T cells through an IDO-dependent mechanism. In addition, CD11c + CD8 + T cells in small intestine, but not in large intestine, were recently identified as a distinct intestinal regulatory T cell population to control proinflammatory CD4 T cells and maintain intestinal mucosal homeostasis (28) …”

Section: Cd4mentioning

confidence: 99%

CD11chighCD8+ Regulatory T Cell Feedback Inhibits CD4 T Cell Immune Response via Fas Ligand–Fas Pathway

Chen

Yun

et al. 2013

The Journal of Immunology

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Regulatory T cells can restrict the uncontrolled immune response and inflammation, avoiding pathologic immune injury to the host and thus playing important roles in the maintenance of immune homeostasis. Until recently, many subsets of CD4 and CD8 regulatory T cells have been reported. In this study, we identified CD11chighCD8+ T cells as a new subset of CD8+ regulatory T cells. During Listeria monocytogenes and Staphylococcus aureus infection, two subsets of CD8 T cells were classified according to the expression level of CD11c, including CD11clowCD8+ and CD11chighCD8+ T cells. CD11clowCD8+ T cells, existing during the whole period of infection, act as conventional activated T cells to kill target cells in a perforin-dependent manner. Interestingly, CD11chighCD8+ T cells appeared only at a late stage of infection, expressed relatively high CD122 and low CD69, did not secrete IFN-γ, IL-10, TGF-β, and exhibited much more potent cytotoxicity against target cells via Fas ligand–Fas pathway in an Ag-independent manner. Ligation of CD11c was important in the cytotoxicity of CD11chighCD8+ T cells. Furthermore, CD11chighCD8+ T cells could directly kill the activated CD4 T cells both in vitro and in vivo, whereas CD11clowCD8+ T cells could not. Thus, we identified an infection-induced new subset of CD11chighCD8+ regulatory T cells, which might contribute to protect host from pathological immune injure. Our results indicate that CD11c+CD8+ T cells are constitute a heterogeneous population that can be divided further into regulatory CD11chighCD8+ T cell subset and effector CD11clowCD8+ T cell subset, thus adding insight to the role of CD8 T cells in immune response and regulation.

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Section: Cd4mentioning

confidence: 99%

CD11chighCD8+ Regulatory T Cell Feedback Inhibits CD4 T Cell Immune Response via Fas Ligand–Fas Pathway

Chen

Yun

et al. 2013

The Journal of Immunology

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“…Although inflammation is seen primarily in the colon in this model, several recent studies have shown that regulatory cell induction in the small intestine is necessary to protect from colitis, leading us to further investigate this decrease in Tregs in the PP and small intestine. 32, 33 …”

Section: Resultsmentioning

confidence: 99%

Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis

2013

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The FVB.mdr1a−/− mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell mediated colitis. In addition, MDR1 polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp3+ regulatory T cells (Treg) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp3+IL-17+ cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTreg), as fewer Foxp3+ iTregs developed from naïve FVB.mdr1a−/− T cells both upon TGF-β treatment in vitro and after adoptive transfer into FVB.rag2−/− recipients. Rather, in vitro TGF-β treatment results in a IL-17+CD4+ T cell. This failure of iTregs to develop explains the decrease in Foxp3+ Tregs in the FVB.mdr1a−/− intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with MDR1 polymorphisms.

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“…Generally, intestinal CD11c + MHC class II + DCs can be divided into three major subsets; CD103 + CD11b 2 , CD103 + CD11b + , and CD103 2 CD11b + cells, and the functions of each subset are intensively analyzed in many studies (15,(28)(29)(30). In this study, we used CD11c-cre transgenic mice to examine the role of DCs and identified magnetically sorted CD11c + cells as DCs, although CD11c is reported to express on other immune cells such as CD8 + T cells in the intestine (31). TGF-b is an important cytokine in the pathogenesis of inflammatory diseases, including IBD (32).…”

Section: Discussionmentioning

confidence: 99%

TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota

Ihara

Hirata

Serizawa

et al. 2016

The Journal of Immunology

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Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-β signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2fl/fl mice developed spontaneous colitis, and CD11c-cre Tgfbr2fl/+ mice exhibited susceptibility to dextran sulfate sodium–induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2fl/fl mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae. Wild-type mice transplanted with CD11c-cre Tgfbr2fl/fl bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion. These findings suggest that TGF-β signaling in DCs regulates intestinal homeostasis by modulating epithelial cell differentiation and fecal microbiota.

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Small intestine CD11c⁺CD8⁺T cells suppress CD4⁺T cell-induced immune colitis

Cited by 27 publications

References 48 publications

CD11chighCD8+ Regulatory T Cell Feedback Inhibits CD4 T Cell Immune Response via Fas Ligand–Fas Pathway

CD11chighCD8+ Regulatory T Cell Feedback Inhibits CD4 T Cell Immune Response via Fas Ligand–Fas Pathway

Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis

TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota

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