Interleukin-7 (IL-7) is a crucial cytokine molecule that regulates the immune response by influencing T and B cell development. It is produced by stromal cells that provide the scaffold for several body tissues, including the thymus, bone marrow, and lymph nodes. IL-7 shows excellent potential as a therapeutic target in immunodeficiency disorders and cancer immunotherapies. 

What Is IL-7?

Discovered by Namen et al. in a pivotal 1988 B cell growth study, scientists quickly recognized IL-7 as a crucial regulator of lymphocyte development and homeostasis in the immune system. It belongs to the common γ-chain (γc) cytokine family, also known as the IL-2 receptor family. 

IL-7 is a pleiotropic cytokine that exerts multiple effects on different cell types. Therefore, its expression is tightly regulated to ensure proper immune system functioning.

IL-7 Synthesis and Receptors

Stromal cells synthesize IL-7 in the bone marrow, thymus, and peripheral lymphoid organs, such as lymph nodes and Peyer’s patches of the small intestine. Tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) induce stromal cells to produce IL-7.

The IL-7 receptor (IL-7R) is a heterodimeric receptor composed of two subunits: the IL-7 receptor alpha chain (IL-7Rα/CD127) and the common γ-chain (γc/CD132). Several other cytokine receptors share the γc chain. 

However, the IL-7Rα chain binds specifically to IL-7. In B and T cells, the IL-7R complex lacks any intrinsic tyrosine kinase signaling activity, so it relies on the Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) families of non-receptor kinases and adaptors to mediate downstream signaling pathways. IL-7Rα is expressed on the surface of immature and mature T cells, early B cells, natural killer (NK) cells, and dendritic cells (DC). 

IL-7 Function in T and B Cell Development

IL-7 is critical to T and B cell development, survival, and homeostasis. In the thymus, IL-7 promotes the survival and proliferation of early T cell progenitors, aiding in the maturation of CD4+ and CD8+ T cells. The presence of IL-7 and corresponding IL-7Rα on the surface of developing T cells creates positive selection pressure on those thymus cells. 

When IL-7Rα binds IL-7 in a T cell’s earliest developmental stages, it triggers the expression of survival factors that prevent the cells from being pushed into programmed cell death. Without IL-7Rα, these cells would succumb to these selection pressures and die before leaving the thymus. 

IL-7 signaling also causes T cell receptors (TCR) to rearrange and gain function. Once this occurs, the expression of IL-7Rα is downregulated and the developing T cell continues into its continuum of maturation, ensuring a diverse and self-tolerant T cell repertoire. 

Similarly, IL-7 supports B cell development in the bone marrow by stimulating the proliferation of B cell progenitors through pro-survival signaling. It regulates B cell receptor rearrangement, creating mature B cells capable of recognizing presented antigens. However, unlike T cells, once B cells reach maturity, they terminate IL-7R expression and become unresponsive to IL-7.

IL-7 Impact on Other Immune Cells

Apart from its effects on T and B cell development, IL-7 influences the survival and homeostasis of several types of immune cells.

  • Naive T cells: As shown by the work of Chu et al., IL-7 supports the proliferation and migration of naive CD4+ and CD8+ T cells throughout the body, enabling them to respond effectively to pathogens upon antigen presentation. 
  • Natural killer cells: NK cells rely on IL-7 for survival and optimal functioning. IL-7 helps sustain NK cell populations and enhances their ability to detect and eliminate infected or abnormal cells through upregulation of the Fas ligand, according to a study by Lum et al. looking at the effects of cytokines on HIV virus immunity. 
  • Dendritic cells: As antigen-presenting cells, DCs are essential for initiating and modulating immune responses using major histocompatibility complex class II (MHC II) surface molecules. As determined by Guimond et al., IL-7 influences DC activity by downregulating the expression of MHC II, which reduces the activation and expansion of CD4+ T cells. This process helps prevent uncontrolled CD4+ T cell expansion in vivo during an immune response. 

IL-7 in Immunotherapy

Given its central role in T and B cell development and homeostasis, IL-7 has attracted attention for its promise in clinical applications. Specifically, IL-7 has shown great potential as an adjuvant in cancer immunotherapies. 

IL-7 enhances T cell survival and proliferation ex vivo, bolstering the efficacy of adoptive T cell therapies like chimeric antigen receptor T cell (CAR-T) therapy. CAR-T therapy involves engineering patients’ T cells to express specific receptors, enabling them to recognize and attack cancer cells more effectively.

In addition, IL-7 immunotherapy is a promising approach to treating immunodeficiency disorders, such as severe combined immunodeficiency (SCID) and acquired immunodeficiency syndrome (AIDS). As research on IL-7 continues, more breakthroughs that lead to improved treatments for many diseases and conditions can be expected.

IL-7 and IL-15: Synergy in Immune Cell Activation

IL-7 and IL-15 are members of the common γ-chain cytokine family and share similarities in their signaling pathways. They are often combined ex vivo to create cytokine-enriched growth media for expanding immune cells. 

While both cytokines are crucial for T cell development and survival, IL-15 also plays a significant role in the homeostasis and activation of memory CD8+ T cells and NK cells. By adding IL-15 to the ex vivo culture, researchers can selectively expand these subsets, essential for mounting robust and durable immune responses against infections and cancer cells. 

Combining IL-7 and IL-15 in the ex vivo expansion process can lead to a synergistic effect, resulting in a more potent pool of immune cells. Both cytokines enhance the survival, proliferation, and function of various T cell populations, including naïve and stem cell memory T cells (TSCM). These expanded and enriched immune cell populations can then be infused back into the patient, leading to a more effective and targeted immune response against the disease.

Nanotein Harnesses IL-7 for Cell Activation

Nanotein Technologies’ IL-7 & IL-15 CAR-T expansion protocols take advantage of the synergistic action of these two cytokines. By combining Nanotein’s activator technology with IL-7 and IL-15 supplemented culture medium, researchers can greatly enhance the proliferation and survival of their engineered CAR-T cells, leading to improved anti-tumor responses. This process works particularly well with the NanoSpark™ STEM-T Soluble T Cell Activator, improving the success of your CAR-T therapy in various cancer types. 

Contact our team today to learn more about integrating NanoSpark activators and IL-7/IL-15 into your cell therapy research. 

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