Perspectives of the relationship between IL-7 and autoimmune diseases

Abstract

Interleukin (IL)-7 is one of the IL-2 family cytokines comprised of IL-2, IL-4, IL-7, IL-9, IL-15, as well as IL-21. IL-7 is mainly secreted by stroma cells in primary lymphoid tissues, playing an essential role in the program of T cell development. Recently, studies have revealed that physiological function exerted by immunocytes can be influenced by aberrant IL-7 signaling, which is common in abnormal autoimmunity regulation. There is also increasing evidence that IL-7 is involved in several autoimmune diseases, such as rheumatoid arthritis, type I diabetes, multiple sclerosis and systemic lupus erythematosus, etc. Targeting components in IL-7 signaling pathways may have potential significance for treating numerous autoimmune diseases. In this review, we therefore summarize our current understandings regarding the relationship between IL-7 and autoimmune diseases so as to render more valuable information on this kind of research.

Decreased serum level of IL-7 in patients with active Graves’ disease

“…IL-7 signaling, initiated with receptor heterodimerization, involves a number of tyrosine kinase pathways associated with the cytoplasmic tail of the receptor. These include the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway, phosphatidylinositol 3-kinase (PI3-kinase) and Src family tyrosine kinases pathway [1,2,5]. Besides the cell-associated form of the IL-7 receptor, human plasma-soluble forms such as sIL-7Ra and scc have also been detected, with the levels of sIL-7Ra being higher than those of scc [6].…”

“…IL-7 provides a survival and proliferation signal in the early stages of T cell development (CD4 À CD8 À double negative cells). These are followed by suppression of IL-7 signal transduction in the preselection of double positive thymocytes and its restoration after positive selection [1]. Although IL-7 is best known for its effects on developing T cell populations, it also modulates peripheral T cell functions via multifactorial mechanisms.…”

“…Human IL-7 is a 25 kDa glycoprotein [2] which was first discovered in 1988 as a factor that promoted the growth of murine B cell precursors in a bone marrow culture system [3]. IL-7 secretion has been detected mainly in stromal cells, including epithelial cells in thymus and bone marrow [1]. In addition, intestinal epithelial cells, keratinocytes, hepatic tissue, peripheral blood dendritic cells, follicular dendritic cells, endothelial cells, smooth muscle cells and fibroblasts have also been shown to produce IL-7 [2].…”

“…Interleukin (IL)-7 is a cytokine of IL-2 family, which also includes IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 [1]. Human IL-7 is a 25 kDa glycoprotein [2] which was first discovered in 1988 as a factor that promoted the growth of murine B cell precursors in a bone marrow culture system [3].…”

“…Both chains of IL-7R are needed for IL-7 signaling transduction [1,2]. IL-7 signaling, initiated with receptor heterodimerization, involves a number of tyrosine kinase pathways associated with the cytoplasmic tail of the receptor.…”