FcεRI Induces the Tryptophan Degradation Pathway Involved in Regulating T Cell Responses

Bubnoff, Dagmar von; Matz, Heike; Frahnert, Christine; Rao, Marie Luise; Hanau, Daniel; Salle, Henri; Bieber, Thomas

doi:10.4049/jimmunol.169.4.1810

Cited by 90 publications

(86 citation statements)

References 37 publications

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“…The total RNA of HGFs after 12 h of stimulation with TLR ligand(s) and/or cytokine was reverse transcribed and treated with DNase I as previously mentioned. IDO was amplified using specific primer (5Ј-CTTCCTGGTCTCTCTATTGG-3Ј/5Ј-GAAGTTCCTGTGAGCTGGT-3Ј; Sigma-Aldrich) (21). The expected size of the PCR product was 430 bp.…”

Section: Mrna Expression Of Idomentioning

confidence: 99%

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

130

104

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Human gingival fibroblasts (HGFs), a predominant cell type in tooth-supporting structure, are presently recognized for their active role in the innate immune response. They produce a variety of inflammatory cytokines in response to microbial components such as LPS from the key periodontal pathogen, Porphyromonas gingivalis. In this study, we demonstrated that HGFs expressed mRNA of TLRs 1, 2, 3, 4, 5, 6, and 9, but not TLRs 7, 8, and 10. Stimulation of HGFs with highly purified TLR2 ligand (P. gingivalis LPS), TLR3 ligand (poly(I:C)), TLR4 ligand (Escherichia coli LPS), and TLR5 ligand (Salmonella typhimurium flagellin) led to expression of IL-8 and IDO. A potent TLR 9 ligand, CpG oligodeoxynucleotide 2006 had no effect, although HGFs showed a detectable TLR9 mRNA expression. No significant enhancement on IL-8 or IDO expression was observed when HGFs were stimulated with various combinations of TLR ligands. Surprisingly, the TLR9 ligand CpG oligodeoxynucleotide 2006 was able to specifically inhibit poly(I:C)-induced IL-8 and IDO expression. TNF-α enhanced TLR ligand-induced IL-8 production in HGFs, whereas IFN-γ enhanced TLR ligand-induced IDO expression. HGF production of IDO in response to P. gingivalis LPS, IFN-γ, or the two in combination inhibited T cell proliferation in MLRs. The observed T cell inhibition could be reversed by addition of either 1-methyl-dl-tryptophan or l-tryptophan. Our results suggest an important role of HGFs not only in orchestrating the innate immune response, but also in dampening potentially harmful hyperactive inflammation in periodontal tissue.

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Section: Mrna Expression Of Idomentioning

confidence: 99%

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

130

104

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“…Sections were analyzed on an Olympus IX71 inverted microscope (Olympus, Hamburg, Germany). The ratio of L-kynurenine/L-tryptophan in serum, an indicator of IDO activity, was quantified by HPLC (Shimadzu, Duisburg, Germany) as previously described [33]. IDO activity was blocked using the competitive inhibitor D-isomer of 1-methyl-tryptophan (1-MT; Sigma).…”

Section: Antibody Responsesmentioning

confidence: 99%

Systemic application of CpG‐rich DNA suppresses adaptive T cell immunity via induction of IDO

et al. 2005

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CpG-rich oligonucleotides (CpG-ODN) bind to Toll-like receptor 9 (TLR9) and are used as powerful adjuvants for vaccination. Here we report that CpG-ODN not only act as immune stimulatory agents but can also induce strong immune suppression depending on the anatomical location of application. In agreement with the adjuvant effect, subcutaneous application of antigen plus CpG-ODN resulted in antigen-specific T cell activation in local lymph nodes. In contrast, systemic application of CpG-ODN resulted in suppression of T cell expansion and CTL activity in the spleen. The suppressive effect was mediated by indoleamine 2,3-dioxygenase (IDO) as indicated by the observation that CpG-ODN induced IDO in the spleen and that T cell suppression could be abrogated by 1-methyl-tryptophan (1-MT), an inhibitor of IDO. No expression of IDO was observed in lymph nodes after injection of CpG-ODN, explaining why suppression was restricted to the spleen. Studies with a set of knockout mice demonstrated that the CpG-ODN-induced immune suppression is dependent on TLR9 stimulation and independent of type I and type II interferons. The present study shows that for the use of CpG-ODN as an adjuvant in vaccines, the route of application is crucial and needs to be considered. In addition, the results indicate that down-modulation of immune responses by CpG-ODN may be possible in certain pathological conditions. See accompanying commentary: http://dx

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“…Most interestingly, oral LC exhibit a dramatically increased expression of FceRI on their cellular surface, which is only partially occupied with IgE molecules (74) ( Table 1). In view of rising evidence for a major role of FceRI on APC, which besides its pro-inflammatory properties is even capable of initiating anti-inflammatory signals, such as the release of IL-10 and the induction of IDO (75)(76)(77), it is tempting to speculate that engagement of FceRI by allergens on LC of the oral mucosa contributes to the tolerogenic properties of this cell type. Furthermore the developments of the past years have uncovered the existence of a sophisticated machinery that allows mucosal DC to induce tolerance induction within their tissue of residence.…”

Section: Antigen Presenting Cells Of the Oral Mucosamentioning

confidence: 99%

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

Novak

Allam

Betten

et al. 2003

Allergy

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It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti‐inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro‐inflammatory reactions and actively induce a T‐cell response, yet on the other hand they serve an important function as ‘silencers’ in the immune system by sending out anti‐inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both – accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.

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FcεRI Induces the Tryptophan Degradation Pathway Involved in Regulating T Cell Responses

Cited by 90 publications

References 37 publications

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Systemic application of CpG‐rich DNA suppresses adaptive T cell immunity via induction of IDO

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

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