T-helper 17 type immune response

Definition

Target type: biologicalprocess

An immune response which is associated with resistance to intracellular bacteria with a key role in inflammation and tissue injury. This immune response is associated with pathological autoimmune conditions such as multiple sclerosis, arthritis and psoriasis which is typically orchestrated by the production of particular cytokines by T-helper 17 cells, most notably interleukin-17, IL-21 and IL-22. [GOC:BHF, GOC:ebc]

T helper 17 (Th17) cells are a subset of CD4+ T lymphocytes that play a crucial role in the immune response against extracellular pathogens, such as bacteria and fungi, and in the pathogenesis of autoimmune diseases. They are characterized by their production of signature cytokines, including interleukin-17 (IL-17), IL-21, and IL-22.

The differentiation of naive CD4+ T cells into Th17 cells is a complex process that involves the coordinated action of various signaling pathways and transcription factors. The process begins with the recognition of an antigen by the T cell receptor (TCR) on the surface of the naive CD4+ T cell. This recognition event, in the context of the appropriate co-stimulatory signals, initiates a signaling cascade that leads to the activation of transcription factors, such as STAT3 and RORγt.

Several factors contribute to the polarization of naive CD4+ T cells towards the Th17 lineage:

1. **Cytokine Environment:** The cytokine environment in which the naive CD4+ T cell encounters the antigen plays a critical role in determining its fate. The presence of the pro-inflammatory cytokines IL-6, IL-21, and TGF-β is essential for Th17 differentiation.
2. **Transcription Factors:** Key transcription factors involved in Th17 differentiation include RORγt, STAT3, and BATF. RORγt is a master regulator of Th17 development, while STAT3 is activated by IL-6 signaling. BATF cooperates with RORγt to enhance Th17 cell differentiation.
3. **Microenvironment:** The presence of commensal bacteria in the gut is also important for Th17 cell development. Specific commensal bacteria produce metabolites that can induce the expression of RORγt and promote Th17 cell differentiation.

Once differentiated, Th17 cells exert their effects through the production of various cytokines, primarily IL-17, IL-21, and IL-22.

1. **IL-17:** IL-17 is a pro-inflammatory cytokine that plays a critical role in the recruitment and activation of neutrophils, a type of white blood cell that is important for fighting bacterial and fungal infections. IL-17 also promotes the production of chemokines and other pro-inflammatory mediators, further amplifying the inflammatory response.
2. **IL-21:** IL-21 is a cytokine that has both autocrine and paracrine functions. It can act on Th17 cells themselves to enhance their survival and proliferation, and it can also act on other immune cells, such as B cells, to promote antibody production.
3. **IL-22:** IL-22 is a cytokine that primarily targets epithelial cells, playing a role in epithelial cell proliferation and repair, and in the production of antimicrobial peptides.

Th17 cells are involved in various physiological processes, including:

1. **Defense Against Extracellular Pathogens:** Th17 cells play a crucial role in host defense against extracellular pathogens, such as bacteria and fungi. They contribute to the clearance of these pathogens by promoting the recruitment of neutrophils and other inflammatory cells to the site of infection.
2. **Tissue Repair:** IL-22 produced by Th17 cells is involved in tissue repair and regeneration. It promotes the proliferation and survival of epithelial cells, aiding in the restoration of damaged tissue after infection or injury.
3. **Autoimmune Diseases:** Th17 cells have been implicated in the pathogenesis of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Dysregulation of Th17 cell function can lead to an excessive inflammatory response, contributing to the development of these diseases.

The balance between Th17 cell responses and other immune cells is critical for maintaining immune homeostasis. Inappropriate Th17 cell activation can lead to chronic inflammation and disease. Understanding the intricate pathways involved in Th17 cell differentiation and function is essential for developing novel therapeutic strategies for treating autoimmune diseases and infectious diseases.'
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Proteins (2)

Compounds (29)