T-helper 2 cell differentiation

Definition

Target type: biologicalprocess

The process in which a relatively unspecialized T cell acquires specialized features of a T-helper 2 (Th2) cell. A Th2 cell is a CD4-positive, alpha-beta T cell that has the phenotype GATA-3-positive and produces interleukin-4. [CL:0000546, GOC:ebc]

T-helper 2 (Th2) cell differentiation is a crucial process in the adaptive immune response, responsible for orchestrating allergic and parasitic responses. It involves a complex interplay of signals, including cytokines, transcription factors, and cell-cell interactions, ultimately driving the commitment of naive CD4+ T cells into Th2 cells. Here's a detailed breakdown:

1. **Initial Activation:** Naive CD4+ T cells encounter antigen presented by antigen-presenting cells (APCs), such as dendritic cells, in the context of MHC Class II molecules. This interaction initiates TCR signaling, leading to the activation and proliferation of the naive T cells.

2. **Cytokine Environment:** The cytokine milieu surrounding the activated T cell plays a critical role in directing its differentiation pathway. IL-4, produced by various cell types including basophils, mast cells, and other Th2 cells, is a key cytokine driving Th2 differentiation.

3. **Transcription Factor Activation:** IL-4 signaling activates the transcription factor STAT6, which plays a pivotal role in Th2 commitment. STAT6 induces the expression of GATA3, another crucial transcription factor essential for Th2 cell development and function.

4. **Th2 Cell Commitment:** GATA3, in turn, promotes the expression of a range of genes characteristic of Th2 cells, including:
* **Cytokine Production:** IL-4, IL-5, and IL-13, the hallmark cytokines of Th2 cells, are responsible for eliciting allergic and parasitic responses. IL-4 promotes IgE production by B cells, IL-5 supports eosinophil differentiation and activation, and IL-13 contributes to mucus production and smooth muscle contraction in the airways.
* **Surface Receptors:** Th2 cells express high levels of the IL-4 receptor (IL-4Rα) and the IL-5 receptor (IL-5Rα), enhancing their responsiveness to these cytokines.
* **Transcription Factors:** Th2 cells also maintain high levels of GATA3 and the transcription factor c-Maf, further reinforcing their Th2 identity.

5. **Effector Function:** Fully differentiated Th2 cells migrate to peripheral tissues, where they engage in their effector functions. They release cytokines that orchestrate allergic responses, such as airway inflammation in asthma and allergic rhinitis, and contribute to the expulsion of parasitic worms from the body.

6. **Regulation:** The differentiation and function of Th2 cells are tightly regulated to maintain immune homeostasis. Regulatory T cells (Tregs) and other immune cells can suppress Th2 cell activity, preventing excessive inflammation.

Overall, Th2 cell differentiation is a tightly controlled process that ensures a balanced immune response. It is essential for mounting protective immunity against parasitic infections but can also contribute to the pathogenesis of allergic diseases.'
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Proteins (3)

Compounds (14)