Immunomodulation by mucosal gene transfer using TGF-beta DNA.

Kuklin, Nelly A.; Daheshia, Massoud; Chun, Sangjun; Rouse, Barry T.

doi:10.1172/jci2803

Cited by 33 publications

(21 citation statements)

References 24 publications

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“…This finding was further substantiated by results showing that nasal administration of naked GFP plasmid DNA resulted in the expression of GFP-positive DCs but not of macrophages and B cells in the intestinal tract, NALT, and spleen. Although the efficacy of the nasal administration of naked DNA was previously reported using Flt3 ligand and TGF-␤ DNA plasmid (23,25), our study is the first to show that expression of nasal DNA occurs in distant mucosal compartments at the single cell level (e.g., IL-12p70-producing large intestinal DCs) and to link that expression to the prevention and treatment of intestinal allergic diseases. Taken together, these data show that noninvasive nasal administration with naked DNA plasmid results in the expression of the corresponding protein in both the mucosal and systemic lymphoid tissues and so may offer a new avenue of therapy for mucosa-associated diseases.…”

Section: Discussionmentioning

confidence: 61%

“…Gene therapy has recently been used both experimentally and clinically as a tool for developing new vaccines or for halting the progression of immunological diseases. Nasal TGF-␤ DNA plasmid has been shown to be effective in mitigating the severity of ocular and intestinal inflammatory diseases (23,24) The administration of Fms-like tyrosine kinase-3 (Flt3) ligand DNA has also been shown to increase the number of activated lymphoid DCs and to thereby induce Agspecific mucosal and systemic Ab responses (25). Although the mucosal delivery of naked DNA specific for regulatory molecules has been shown to be effective for the modulation of immune responses, the fate of the mucosally delivered naked DNA and its efficacy in inducing and regulating immune responses at distant sites remains unknown.…”

mentioning

confidence: 99%

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Nasal IL-12p70 DNA Prevents and Treats Intestinal Allergic Diarrhea

Hino

Fukuyama²,

Kataoka³

et al. 2005

The Journal of Immunology

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OVA-induced allergic diarrhea occurs as a consequence of over-expression of Th1 inhibitory IL-12p40 monomers and homodimers in the large intestine, establishing a dominant Th2-type environment. In this study, we demonstrate that intranasally administered murine IL-12p70 naked DNA expression plasmids resulted in the synthesis of corresponding cytokine in the large intestinal CD11c+ dendritic cells, leading to the inhibition of Ag-specific Th2-type response for the prevention of allergic diarrhea and the suppression of clinical symptoms including OVA-specific IgE Ab synthesis. The nasal IL-12p70 DNA treatment proved effective even after the establishment of allergic diarrhea. These results suggest that the mucosal administration of naked IL-12p70 DNA plasmid should be considered as a possible preventive and therapeutic treatment for Th2 cell-mediated food allergic diseases in the intestinal tract.

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Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

Nasal IL-12p70 DNA Prevents and Treats Intestinal Allergic Diarrhea

Hino

Fukuyama²,

Kataoka³

et al. 2005

The Journal of Immunology

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“…The method used was described in detail previously (23). Splenocytes from subcutaneously or orally immunized animals were analyzed for IFN-γ spot-forming (SF) cells.…”

Section: Methodsmentioning

confidence: 99%

α4β7 independent pathway for CD8+ T cell–mediated intestinal immunity to rotavirus

Kuklin¹,

Rott²,

Darling³

et al. 2000

J. Clin. Invest.

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“…Lesions in some animals resolve without treatment and in such cases the cytokine IL-10 is up-regulated (4). In addition, expression of IL-10 or TGF-␤ early in the experimental disease may alleviate lesion severity (5,6). Whether or not dedicated cell types that produce anti-inflammatory cytokines enter the cornea and regulate responses has not been explored.…”

Section: Cd4mentioning

confidence: 99%

CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions

Suvas

Azkur

Kim

et al. 2004

The Journal of Immunology

316

302

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CD4+CD25+ regulatory T cells (Treg) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of Treg in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of Treg before infection. The Treg was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4+ T cells in infected SCID recipients. The mechanism of Treg control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, Treg isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of Treg in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.

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Immunomodulation by mucosal gene transfer using TGF-beta DNA.

Cited by 33 publications

References 24 publications

Nasal IL-12p70 DNA Prevents and Treats Intestinal Allergic Diarrhea

Nasal IL-12p70 DNA Prevents and Treats Intestinal Allergic Diarrhea

α4β7 independent pathway for CD8+ T cell–mediated intestinal immunity to rotavirus

CD4+CD25+ Regulatory T Cells Control the Severity of Viral Immunoinflammatory Lesions

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