HGNC Approved Gene Symbol: IL11
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38): 19:55,364,382-55,370,463 (from NCBI)
Paul et al. (1990) identified and cloned the gene for a novel stromal cell-derived lymphopoietic and hematopoietic cytokine that they called interleukin-11. The cDNA indicated a single reading frame encoding a predicted 199-amino acid polypeptide. The IL11 produced in COS-1 cells showed an apparent molecular mass of about 23 kD.
Biologic characterization by Paul et al. (1990) indicated that, in addition to stimulating plasmacytoma proliferation, IL11 stimulates T-cell-dependent development of immunoglobulin-producing B cells and collaborates with IL3 (147740) in supporting murine megakaryocyte colony formation.
Du and Williams (1994) reviewed the pleiotropic effects of IL11 on hematopoietic cells.
Du and Williams (1997) reviewed the molecular, cell biologic, and clinical aspects of interleukin-11.
Cytokines in the IL11 subfamily participate in the regulation of bone cell proliferation and differentiation. Takeuchi et al. (2002) reported positive effects of IL11 on osteoblasts and bone formation. In transgenic mice, overexpression of the human IL11 gene resulted in the stimulation of bone formation to increase cortical thickness and strength of long bones.
Schafer et al. (2017) used integrated imaging-genomics analyses of primary human fibroblasts, that upregulation of IL11 is the dominant transcriptional response to TGF-beta-1 (190180) exposure and required for its profibrotic effect. IL11 and its receptor, IL11RA (600939), are expressed specifically in fibroblasts, in which they drive noncanonical, extracellular signal-regulated kinase (ERK; see 176872)-dependent autocrine signaling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure, whereas genetic deletion of Il11ra1 protects against disease. Therefore, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important profibrotic stimuli. Schafer et al. (2017) concluded that their results revealed a central role of IL11 in fibrosis.
McKinley et al. (1992) determined that the genomic sequence of IL11 is 7 kb long and consists of 5 exons and 4 introns.
Yang-Feng et al. (1991) demonstrated by in situ hybridization that a cDNA for IL11 maps to 19q13.3-q13.4. Since translocations involving 19q13 occur in patients with acute lymphocytic leukemia, the IL11 gene may be implicated.
IL13 (147683) is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation. Chen et al. (2005) found that transgenic mice overexpressing Il13 specifically in lung showed upregulation of both Il11 and Il11ra (600939), but not Il6r (147880), as well as upregulation of other IL6 (147620)-type cytokines and a modest increase in gp130 (IL6ST; 600694). Il13 transgenic Il11ra -/- mice exhibited a decrease in the inflammatory response seen in Il13 transgenic Il13ra +/+ mice, as well as reduced fibrosis, hyaluronic acid accumulation, chemokine production, and alveolar remodeling response. Il13 transgenic Il11ra -/- mice also survived significantly longer than Il13 transgenic Il11ra +/+ mice. Chen et al. (2005) concluded that IL11RA plays a key role in the pathogenesis of IL13-induced inflammation and remodeling. They proposed that IL11, which is induced simultaneously with IL13 in inflammatory disorders such as asthma, may mediate the tissue effects of IL13.
Chen, Q., Rabach, L., Noble, P., Zheng, T., Lee, C. G., Homer, R. J., Elias, J. A. IL-11 receptor alpha in the pathogenesis of IL-13-induced inflammation and remodeling. J. Immun. 174: 2305-2313, 2005. [PubMed: 15699166] [Full Text: https://doi.org/10.4049/jimmunol.174.4.2305]
Du, X., Williams, D. A. Interleukin-11: review of molecular, cell biology, and clinical use. Blood 89: 3897-3908, 1997. [PubMed: 9166826]
Du, X. X., Williams, D. A. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood 83: 2023-2030, 1994. [PubMed: 7512836]
McKinley, D., Wu, Q., Yang-Feng, T., Yang, Y.-C. Genomic sequence and chromosomal location of human interleukin-11 gene (IL11). Genomics 13: 814-819, 1992. [PubMed: 1386338] [Full Text: https://doi.org/10.1016/0888-7543(92)90158-o]
Paul, S. R., Bennett, F., Calvetti, J. A., Kelleher, K., Wood, C. R., O'Hara, R. M., Jr., Leary, A. C., Sibley, B., Clark, S. C., Williams, D. A., Yang, Y.-C. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc. Nat. Acad. Sci. 87: 7512-7516, 1990. [PubMed: 2145578] [Full Text: https://doi.org/10.1073/pnas.87.19.7512]
Schafer, S., Viswanathan, S., Widjaja, A. A., Lim, W.-W., Moreno-Moral, A., DeLaughter, D. M., Ng, B., Patone, G., Chow, K., Khin, E., Tan, J., Chothani, S. P., and 36 others. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature 552: 110-115, 2017. [PubMed: 29160304] [Full Text: https://doi.org/10.1038/nature24676]
Takeuchi, Y., Watanabe, S., Ishii, G., Takeda, S., Nakayama, K., Fukumoto, S., Kaneta, Y., Inoue, D., Matsumoto, T., Harigaya, K., Fujita, T. Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice. J. Biol. Chem. 277: 49011-49018, 2002. [PubMed: 12384500] [Full Text: https://doi.org/10.1074/jbc.M207804200]
Yang-Feng, T. L., Gibson, L., Yang, Y. C. Assignment of the gene encoding human interleukin-11 to chromosome 19q13.3-q13.4. (Abstract) Cytogenet. Cell Genet. 58: 2027 only, 1991.