Interleukin-9

Interleukin-9 (IL-9) is a cytokine that is produced by T-helper cells. The cytokine is a 14kD glycoprotein with 144 amino acids. Interleukin-9 is encoded by the interleukin-9 gene located on chromosome 5. Interleukin-9 is primarily produced by T cells (Th9 cells), mast cells, eosinophilic granulocytes and "innate like lymphoid cells" 2.

Its biological effect is mediated by a membrane-bound specific interleukin-9 receptor (IL-9R). On sensitive cells, the receptor density is approximately 3,000 per cell. Besides the membrane-bound receptor, a soluble receptor type (sIL-9R) is also described.

The effect of interleukin-9 leads via the transcription factors of the NFAT family (activation of NF-κB and BATF as well as the transcription factor IRF49).

In the organism, interleukin-9 is responsible for many physiological and pathophysiological processes. The cytokine acts on cells inside and outside the haematopoietic system.

In the absence of antigens, interleukin-9 stimulates the proliferation of certain subpopulations of T-helper cells, such as the even less known Th9 cells. The cytokine enhances, coaddiditv with interleukin-4, the production of IgG, IgM and IgE by B lymphocytes. Furthermore, interleukin-9 stimulates the proliferation of mast cells. The cytokine induces the formation of precursor cells of erythropoiesis and, together with erythropoietin, leads to the maturation of erythrocytes.

Bronchial asthma: In lung tissue biopsies of patients with bronchial asthma an increased production of interleukin-9 was found. In an experimental asthma approach, the effect of interleukin-9 could be demonstrated on pulmonary mast cells as well as on goblet cells of the lung epithelium and on smooth muscle cells. Increased secretion of IL-9 results in increased mucus secretion, mast cell proliferation and eosinophilia.

Ulcerative colitis: In ulcerative colitis, interleukin-9 has an inductive effect. An increased concentration of IL-9 has been detected in T-cells of patients. Apparently, this is a subpopulation of T-helper cells, so-called Th9 cells. A reduction of this cell population by means of appropriate antibodies is regarded as a therapeutic option for chronic inflammatory bowel disease (CED).

Parasites: IL-9 has a protective effect on parasite defence in the intestine. The protective effect is mainly based on the activation of mucosal mast cells by interleukin-9, which, after activation, secrete various mediators that cause increased contraction, mucus production and eosinophilia, thus promoting parasite excretion.

Autoimmune diseases: Th9 cells and interleukin-9 play an essential role in the pathogenesis of autoimmune diseases such as SLE, progressive scleroderma and experimental autoimmune encephalomyelitis (EAE).

Tumor diseases: Interleukin-9 has a dual action in malignant tumors. An increased production of interleukin-9 could be found in Hodgkin cell lines. Interleukin-9 is a growth factor for T cell lines. Experimentally, a promoting role for the spontaneous development of lymphoblastic lymphomas could be observed in IL-9. Lymphoma cells of patients with T cell leukemia produce predominantly interleukin-9.

Melanoma: In murine melanoma models a protective effect of interleukin-9 has been demonstrated. In the tumor parenchyma mainly mast cells were described as effector cells after interleukin-9 activation. In another melanoma model, interleukin-9 mediated a recruitment of cytotoxic CD8+T cells and CD8+ dendritic cells (DC).

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2. Lv X et al. (2012) The role of interleukin-9 in lymphoma. Leuk lymphoma 54:1367-1372.

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