negative regulation of myeloid dendritic cell activation

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of myeloid dendritic cell activation. [GOC:mah]

Negative regulation of myeloid dendritic cell activation is a complex and tightly controlled process essential for maintaining immune homeostasis and preventing excessive inflammation. It involves a multifaceted interplay of signaling pathways, transcription factors, and inhibitory receptors that dampen the activation of myeloid dendritic cells (mDCs) in response to various stimuli.

mDCs are professional antigen-presenting cells that play a critical role in initiating and shaping immune responses. Upon encountering pathogens or danger signals, they undergo activation, characterized by increased expression of surface receptors, cytokine production, and antigen presentation. However, uncontrolled mDC activation can lead to autoimmune disorders and chronic inflammation. Therefore, negative regulation is crucial to ensure appropriate immune responses and prevent excessive inflammation.

Several mechanisms contribute to the negative regulation of mDC activation, including:

1. **Inhibitory receptors:** mDCs express a range of inhibitory receptors that upon ligand binding, trigger signaling cascades leading to the downregulation of activation pathways. Examples include:
* **Programmed death-1 (PD-1):** Its engagement by PD-L1 and PD-L2 on target cells inhibits mDC activation and cytokine production.
* **CTLA-4:** Interaction with CD80 and CD86 on antigen-presenting cells attenuates mDC activation and T cell costimulation.
* **FcγRIIB:** This receptor on mDCs interacts with immune complexes and induces inhibitory signals, suppressing mDC activation.
2. **Cytokine signaling:** Certain cytokines, such as IL-10 and TGF-β, can suppress mDC activation by directly inhibiting signaling pathways involved in their activation or by promoting the expression of inhibitory receptors.
3. **Transcription factors:** Transcription factors like STAT3 and Foxp3 can regulate the expression of inhibitory receptors or suppress the expression of pro-inflammatory genes involved in mDC activation.
4. **Microenvironment:** The surrounding microenvironment can influence mDC activation. For instance, the presence of regulatory T cells (Tregs) can secrete suppressive cytokines like IL-10, dampening mDC activation.
5. **Metabolic reprogramming:** mDC activation is tightly linked to metabolic changes. Upon activation, mDCs undergo metabolic reprogramming to support their activation and effector functions. However, negative regulatory signals can induce metabolic changes that suppress mDC activation.

Overall, the negative regulation of myeloid dendritic cell activation is a crucial process that involves a complex interplay of molecular mechanisms. It ensures appropriate immune responses, prevents excessive inflammation, and maintains immune homeostasis.'
"

Proteins (2)

Compounds (2)