Exogenous IL-9 Ameliorates Experimental Autoimmune Myasthenia Gravis Symptoms in Rats.

Interleukin-9 (IL-9) is a multifunctional cytokine involved in protective immunity or immunopathology depending on the microenvironment and specific disease settings. Our early study determined that IL-9 and Th9 cells participate in and promote the progression of experimental autoimmune myasthenia gravis (EAMG). The data from this study showed that exogenous recombinant rat IL-9 (rrIL-9) acted as an IL-9 receptor antagonist, reduced the incidence of EAMG in rats, alleviated the severity of the disease, and reduced the anti-acetylcholine receptor (AChR) IgG antibody levels by altering the Th-subset distribution. These data suggest that administration of rrIL-9 may provide a novel therapeutic strategy against MG or related autoimmune diseases. Abbreviations: 2-Mercaptoethanol (2-ME); antibodies (Abs); ?-bungarotoxin (?-BTX); acetylcholine receptor (AChR); airway hyper-reactivity (AHR); allophycocyanin-conjugated (APC); antigen presenting cells (APCs); complete Freund's adjuvant (CFA); Cyanine dye 3 (Cy3); dendritic cells (DCs); experimental autoimmune encephalomyelitis (EAE); experimental autoimmune myasthenia gravis (EAMG); flow cytometry (FACS); fetal bovine serum (FBS); fetal calf serum (FCS); Fluorescein isothiocyanate (FITC); gamma chain (?c); intraperitoneally (i.p.); Incomplete Freund's adjuvant (IFA); interferon (IFN); immunoglobulin (Ig); Interleukin (IL); Janus kinase (JAK); myasthenia gravis (MG); Mononuclear cells (MNC); neuromuscular junctions (NMJ); optical density (OD); ovalbumin (OVA); phosphate-buffered saline (PBS); phycoerythrin (PE); Peridinin chlorophyll protein complex (Percp); Rat AChR ? subunit (R-AChR97-116); Recombinant Rat (rr); room temperature (RT); signal transducer and activator of transcription (STAT); T helper cells (Th).

IL-9 and its receptor are predominantly involved in the pathogenesis of UC.

OBJECTIVE: Several pathogenic roles attributed over the past two decades to either T helper (Th)1 or Th2 cells are increasingly becoming associated with interleukin (IL)-17 and most recently IL-9 signalling. However, the implication of IL-9 in IBD has not been addressed so far. DESIGN: We investigated the expression of IL-9 and IL-9R by using peripheral blood, biopsies and surgical samples. We addressed the functional role of IL-9 signalling by analysis of downstream effector proteins. Using Caco-2 cell monolayers we followed the effect of IL-9 on wound healing. RESULTS: IL-9 mRNA expression was significantly increased in inflamed samples from patients with UC as compared with controls. CD3(+) T cells were major IL-9-expressing cells and some polymorphonuclear leucocytes (PMN) also expressed IL-9. IL-9 was co-localised with the key Th9 transcription factors interferon regulatory factor 4 and PU.1. Systemically, IL-9 was abundantly produced by activated peripheral blood lymphocytes, whereas its receptor was overexpressed on gut resident and circulating PMN. IL-9 stimulation of the latter induced IL-8 production in a dose-dependent manner and rendered PMN resistant to apoptosis suggesting a functional role for IL-9R signalling in the propagation of gut inflammation. Furthermore, IL-9R was overexpressed on gut epithelial cells and IL-9 induced STAT5 activation in these cells. Moreover, IL-9 inhibited the growth of Caco-2 epithelial cell monolayers in wound healing experiments. CONCLUSIONS: Our results provide evidence that IL-9 is predominantly involved in the pathogenesis of UC suggesting that targeting IL-9 might become a therapeutic option for patients with UC.