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Guide to understanding Th1 and Th2 cells

In this guide, we will discuss the differences between Th1 and Th2 cells, as well as their roles in immune system function. We will also explore how cytokines and transcription factors contribute to the differentiation of T helper cells. Finally, we will take a look at some common diseases associated with the two types of cells and explore possible treatment options.

What are T helper cells?

T helper cells are a type of lymphocyte that play an important role in the immune system. They are responsible for activating other immune cells to fight off infection or disease. There are two main types of T helper cells, Th1 cells and Th2 cells, each with their own unique functions.

The main function of Th1 cells is to activate the cellular immune response. This involves recruiting macrophages and other effector cells to destroy infected or cancerous cells. The Th1 response is characterized by the production of Interferon gamma (IFNγ), a powerful cytokine that helps to activate macrophages and other immune cells.

The main function of Th2 cells is to activate the antibody-mediated immune response. This involves recruiting B cells to produce antibodies that can neutralize or destroy pathogens. The main function of Th2 cells is to produce Interleukin-13 (IL-13), a cytokine that helps to activate B cells and other immune cells.

Role of cytokines in determining the fate of T helper cells

Th cells are activated by cytokines, which are small proteins that act as messengers between cells. There are a number of different cytokines, each with its own role in the immune system. The Th cell response is triggered by a subset of cytokines called Th-cell-activating cytokines or TACs. These cytokines bind to specific receptors on the surface of T helper cells, triggering a cascade of events that leads to the activation and differentiation of these cells.

Cytokines play a major role in determining which type of Th cell will be produced. For example, the cytokine IL-12 is a Th-cell-activating cytokine that promotes the differentiation of Th cells into Th1 cells. On the other hand, the cytokine IL-21 is a Th-cell-inhibiting cytokine that inhibits the differentiation of Th cells into Th1 cells.

Th1 vs Th2 cytokines

Th1 cytokines are a group of pro-inflammatory cytokines that promote the activation of macrophages and other effector cells. These cytokines include IFNγ, Tumor Necrosis Factor alpha (TNFα), and Interleukin-12 (IL-12).

Th2 cytokines are a group of anti-inflammatory cytokines that inhibit the activation of macrophages and other effector cells. These cytokine include IL-21, IL-22, and transforming growth factor beta (TGFβ).

Transcription factors required for T helper cell differentiation

The signalling pathways involved in T helper cell differentiation are complex and not fully understood. However, it is known that a number of different transcription factors and cytokines are involved in this process. Transcription factors are proteins that bind to specific DNA sequences and regulate the expression of genes. Some of the transcription factors involved in Th cell differentiation include T-bet, GATA-binding protein-3 (GATA-3), and Forkhead box protein PIII (FoxpIII).

T-bet is a Th cell specific transcription factor that is required for the development of Th0 cells into effector Th cells. GATA-3 is a general lymphoid transcription factor that is required for both Th cell development and function. FoxpIII is a Th cell specific transcription factor that is required for the development of regulatory T cells. TCF-I is a transcription factor that binds to the promoter region of Th cell genes. TCF-I is activated by Wnt signals, which are signaling molecules that are involved in the development and differentiation of T cells.

STATs (signal transducers and activators of transcription) are a family of proteins that mediate the response to cytokines. There are four members of the STAT family, and each member is activated by a different subset of cytokines. For example, STAT-l is activated by Th1 cytokines like IFNγ, while STAT-IV is activated by Th2 cytokines like IL-21.

Diseases associated with dysregulated Th1 and Th2 responses

There are a number of diseases that can be attributed to differences in T helper cell function. Th1 diseases are characterized by a strong Th1 response, while Th2 diseases are characterized by a weak or absent Th1 response. Th1 cytokines like IFNγ and TNFα promote inflammation, while Th2 cytokines like IL-21 and IL-22 inhibit inflammation.

Th1 diseases

  • Asthma is a chronic lung disease that is characterized by airway obstruction and inflammation. Asthma is a Th1 disease, and the Th1 cytokines IFNγ and TNFα play a key role in the development of this disease.
  • Rheumatoid arthritis and Multiple sclerosis are both chronic inflammatory diseases that are caused by autoimmune reactions to joint tissue and myelin respectively. This autoimmune reaction is mediated by Th1 cytokines like IFNγ and TNFα.

Th2 diseases

  • Allergies are a type of hypersensitivity reaction that is mediated by Th2 cytokines such as IL-21 and IL-22. Allergies can cause a range of symptoms, from mild (rash, hives, itching) to severe (anaphylaxis).
  • Eczema is a chronic skin condition that is characterized by dry, itchy skin. Eczema is a Th2 disease, and the Th2 cytokines IL-21 and IL-22 play a key role in the development of this condition.
  • Psoriasis is a chronic skin condition that is characterized by red, scaly patches on the skin. Psoriasis is thought to be caused by an autoimmune reaction to skin cells. This autoimmune reaction is mediated by Th2 cytokines like IL-21 and IL-22.

Targeting Th1 and Th2 cytokines in autoimmune diseases

The main goal of treatment for autoimmune diseases is to reduce inflammation and prevent tissue damage. In some cases, this can be done with corticosteroids or other immunosuppressive drugs. However, these treatments often have side effects and can only provide temporary relief.

Recent advances in our understanding of Th cell differentiation have led to the development of targeted therapies that specifically target Th cells. These therapies seek to modulate the activity of specific cytokines that are involved in the development of autoimmune diseases. For example, therapies targeting IL-12 and IL-23 are currently being developed for the treatment of psoriasis and Crohn's disease. Similarly, therapies targeting IFNγ are being developed for the of rheumatoid arthritis, multiple sclerosis, and eczema.

 

In conclusion, Th cells play a major role in the immune system by regulating the activation and differentiation of other immune cells. The type of Th cell that is produced depends on the combination of cytokines that are present at any given time. This can determine whether you develop a Th1 or Th2 response, which can lead to either a pro-inflammatory or an anti-inflammatory state. Differentiation of Th cells into specific effector subsets allows for fine tuning of the immune response and helps to ensure that it remains effective against potential threats. While there is still much to learn about how T helper cells contribute to disease, understanding the basics of their differentiation and function is an important step in finding better treatments for these conditions. Thanks for reading!​

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9th Mar 2022 Jahnavi Konduru Naga, Msc

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