Il7, or Interleukin-7, is a cytokine belonging to the family of cytokines with four anti-parallel α helixes that bind Type I cytokine receptors [2]. It is produced mainly by stromal cells in the thymus, bone marrow, and lymphoid organs, and is crucial for the development and homeostatic survival of lymphoid cells. IL7 exerts its functions through the IL-7 receptor, which consists of two chains, IL-7Rα and γc. Signaling occurs mainly through JAK1, JAK3 to STAT5, as well as non-canonical STAT3, STAT1, PI3K/AKT, and MEK/ERK pathways [2].

IL7-deficient mice exhibit severe T cell lymphopenia, highlighting its non-redundant role in T cell survival and homeostasis. T cells need to compete for the limited IL7 produced by radio-resistant stromal cells [1]. Abnormalities in the IL-7 pathway in both humans and mice lead to severe combined immunodeficiency due to lymphopenia. Excessive signaling in mice drives autoimmune diseases, and in humans, it is associated with autoimmune syndromes such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, sarcoidosis, atopic dermatitis, and asthma. Mutations in the IL-7 receptor pathway drive acute lymphoblastic leukemia [2].

In conclusion, Il7 is essential for the survival of various lymphocyte subsets, including immature thymocytes, naïve T-cells, memory T-cells, pro-B-cells, and innate lymphocytes. The study of Il7-deficient mouse models has been instrumental in understanding its role in immunodeficiency, autoimmune diseases, and leukemia. These insights can potentially contribute to the development of therapeutic strategies targeting the Il7 pathway in related disease areas.