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Content archived on 2024-06-18

Immune regulation of NF-kappaB in Dendritic Cell subsets by the ubiquitin editing enzyme A20

Objective

Dendritic cells (DCs) are strategically positioned as sentinels that process antigens and present these to other immune cells, thereby acting as crucial messengers between innate and adaptive immunity. DCs are activated by various receptors, including Toll-like receptors (TLRs) that recognize microbial products. TLR stimulation leads to activation of the transcription factor NF-κB, which is the key regulator of pro-inflammatory genes. NF-κB activation is tightly regulated by ubiquitination, a modification process that targets proteins for proteasomal degradation. The most important negative regulator of NF-κB activation is the ubiquitin-modifying enzyme A20/Tnfaip3. We have recently established an in vivo constitutive NF-κB activation mouse model system by DC-specific A20 gene ablation (using the Cre/loxP system). Our preliminary results demonstrate that A20 in DCs critically controls inflammation in the context of allergy and autoimmunity. Consistent with defective termination of TLR/NF-κB signalling, we found that A20KO DCs manifest an activated phenotype and DC-A20KO mice exhibit increased inflammation and high levels of serum autoantibodies. Remarkably however, DC-A20KO mice are protected from allergic asthma and experimental autoimmune encephalomyelitis. The proposal will provide fundamental knowledge on the effects of NF-κB activation in different DC subsets and should offer a starting point for therapies for inflammatory diseases based on ubiquitin modification.

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-PEOPLE-2011-CIG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
EU contribution
€ 100 000,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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