Disease relevance of Il13

• Il4 and Il13 encode the canonical T helper 2 (TH2) cytokines responsible both for promoting immune responses against extracellular pathogens and, when misregulated, causing allergic and autoimmune disease [1].
• Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4-deficient mice and IL-13-deficient mice, they are abolished only in the combined absence of both cytokines [2].
• Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production [3].
• IL-12 plays a pivotal role in early colitis, whereas its absence and the synthesis of IL-4 and IL-13 in late disease indicate that other immune mechanisms sustain chronic inflammation [4].
• Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis [5].
• The reduction in pulmonary eosinophils correlated with attenuation in IL-13-induced mucus cell metaplasia and collagen deposition [6].
• We show that in the absence of IL-13Ralpha2, IL-13-induced pulmonary inflammation, mucus metaplasia, subepithelial fibrosis, and airway remodeling are significantly augmented [7].

Psychiatry related information on Il13

• Intergenic transcription is not required in Th2 cells to maintain histone acetylation and transcriptional permissiveness at the Il4-Il13 locus [8].

High impact information on Il13

• Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity [9].
• The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281(-/-) mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d(-/-) mice of recombinant IL-13, which directly affects airway smooth muscle cells [9].
• T helper 2 (T(H)2) cells elaborate cytokines, such as interleukin (IL)-4, IL-5, IL-9 and IL-13, which work with toxic mediators of innate immune cells to establish environments that are inhospitable to helminth or arthropod invaders [10].
• IL-10 was not able to compensate for the absence of IL-4/IL-13-activated alternative macrophages [11].
• Macrophage/neutrophil-specific IL-4 receptor alpha-deficient mice (LysM(Cre)IL-4Ralpha(-/flox)) were generated to understand the role of IL-4/IL-13 responsive myeloid cells during Type 2 immune responses [11].

Chemical compound and disease context of Il13

• The ability of IL-13 to increase lung size, alveolar size, and lung compliance, to stimulate pulmonary inflammation, hyaluronic acid accumulation, and tissue fibrosis, and to cause respiratory failure and death were markedly decreased, whereas mucus metaplasia was not altered in CCR2(-/-) mice [12].
• Generation of contact hypersensitivity to dinitrofluorobenzene, which involves Th1 and CD8(+) effector cells, was also intact in IL-13(-/-) mice [13].
• CONCLUSION: These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma [14].
• Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts [15].
• We studied the effects of dexamethasone on eotaxin production, eosinophil accumulation, goblet cell hyperplasia, and AHR after IL-13 administration into the airways of mice in vivo [16].

Biological context of Il13

• As described in this issue of Immunity, Lee et al. have now used a transgenic mouse assay to identify a locus control region (LCR) that supports integration site-independent, copy number-dependent transcription of Il4 and Il13 [17].
• Collectively, these findings indicate a novel role of IL-13 in early myelopoiesis, partially overlapping but also different from that of IL-4 [18].
• To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized [3].
• However, the mechanisms that induce rapid transactivation of the IL-13 gene in response to various types of stimulation have hitherto remained unknown [19].
• Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus [20].

Anatomical context of Il13

• Il4 and Il13, closely linked genes, are expressed monoallelically in TH2 cells [21].
• Deletion of HS IV increased Il4 and Il13 transcription by naive T cells and led to T helper type 2 skewing in vitro [22].
• The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4 [18].
• IL-13 enhanced stem cell factor (SCF)-induced proliferation of Lin-Sca-1+ bone marrow progenitor cells more potently than IL-4 [18].
• Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses [2].

Associations of Il13 with chemical compounds

• An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo [23].
• Tyk2 is a member of the Janus family of protein tyrosine kinases and is activated by a variety of cytokines: IFN-alphabeta, IL-6, IL-10, IL-12, and IL-13 [24].
• The production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated macrophages can be markedly inhibited by the two closely related cytokines, interleukin (IL)-4 and IL-13 [25].
• A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13-treated murine peritoneal macrophages [26].
• Upregulation of interleukin-13 and its receptor in a murine model of bleomycin-induced scleroderma [14].

Physical interactions of Il13

• We propose that X-SCID B cells responses to IL-4 are mediated by an IL-13 receptor complex comprised of the IL-4R alpha chain associated with the recently cloned IL-13R binding protein [27].
• Differentiation of naive T cells into mature Th2 cells is associated with the appearance of a complex pattern of DNase I hypersensitive (DH) sites within the IL-4/IL-13 cytokine gene cluster [28].

Regulatory relationships of Il13

• IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent [29].
• However, IL-13-induced AHR and mucus secretion occurred independently of IL-5 and/or eotaxin [30].
• IL-13 markedly suppressed nitric oxide release and to a lesser extent secretion of the pro-inflammatory cytokine tumor necrosis factor-alpha [31].
• Injection of recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice [32].
• These results demonstrate a novel mechanism whereby IL-4 and IL-13 can suppress mast cell development by inducing the production of an apoptosis-inducing factor from macrophages [33].

Other interactions of Il13

• Based on these probabilities, individual cells randomly express Il4 and Il13 alleles [21].
• Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection [34].
• Indeed, severe fibrosis correlated with a high IL-13 and low IFN-gamma/IL-10 mRNA response [5].
• In contrast, the increase in IL-5 and IL-13 mRNA expression was lower in fgr(-/-) compared with wild-type mice [35].
• The splenocytes from the mice fed with CS produced less interleukin (IL)-5, IL-10, and IL-13 than those from the control group [36].

Analytical, diagnostic and therapeutic context of Il13

• Exogenous administration of interleukin-4 (IL-4) or IL-13 was recently shown to regulate this inflammatory injury in association with activation of signal transducer and activator of transcription-6 (STAT6) [37].
• In addition, the levels of bioactive and total TGF-beta(1) were decreased in lavage fluids from IL-13 transgenic mice with -/- CCR2 loci [12].
• To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR [38].
• Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13 [39].
• Consistent with these observations, a profound reduction of Th2 cytokine production (IL-5 and IL-13) was detected in the bronchoalveolar lavage fluid (BAL) [40].

References