Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis

Ma, Lei; Xue, Haibo; Guan, Xiu-Hao; Shu, Chen; Zhang, J.-H.; Yu, Jianxiu

doi:10.1111/cei.12198

Cited by 101 publications

(101 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent studies revealed a T-cell subset (Th9 cells) that predominantly produces IL-9 and is distinct from the classic Th1, Th2 and Th17 subsets (2-4). Several reports showed that Th9 cells could be involved in the pathogenesis of chronic allergic disorders such as asthma, allergic rhinitis and atopic dermatitis (23,24). Further studies indicated that serum levels of IL-9 are increased in patients with SLE and other autoimmune diseases such as systemic scleroderma (8,25,26).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-9 Is Associated with Elevated Anti-Double-Stranded DNA Antibodies in Lupus-Prone Mice

Yang

et al. 2015

Mol Med

View full text Add to dashboard Cite

Interleukin (IL)-9, which is produced mainly by CD4 + T cells, is implicated in mast cell-related allergic diseases, although its involvement in systemic lupus erythematosus (SLE) pathogenesis remains unclear. Thus, we investigated the presence of IL-9 in lupus-prone MRL/Mp-lpr/lpr (MRL/lpr) mice and examined the role of IL-9 in lupus pathogenesis. Increased levels of IL-9 + lymphocytes were detected in the spleens and kidneys of MRL/lpr mice and increased IL-9 levels in the spleen correlated with PNA + germinal center (GC) cell expansion. The percentage of CD4 + IL-9 + (Th9) cells was increased in MRL/lpr mice and serum IL-9 levels were elevated and closely related to the production of antibodies against double-stranded DNA (dsDNA). IL-9 appears to promote B-cell proliferation and immunoglobulin production, which could be blocked by inhibition of signal transducer and activator of transcription 3 (STAT3). Treatment with neutralizing anti-IL-9 antibody in vivo decreased serum anti-dsDNA-antibody titers and alleviated lupus nephritis in MRL/lpr mice. Our findings indicate expansion of Th9 cells in lupus-prone MRL/lpr mice and the correlation of IL-9 with B-cell proliferation and autoantibody production. These findings suggest that IL-9 is a potential therapeutic target for SLE. autoantibody activity. IL-9 induced B-cell proliferation and immunoglobulin production in vitro, but this effect was blocked by signal transducer and activator of transcription 3 (STAT3) inhibition. Administration of neutralizing antibody against IL-9 in vivo relieved lupus nephritis in MRL/lpr mice. Further study indicated that IL-9 acts synergistically with IL-17 to promote immunoglobulin production in vitro and in vivo. Our data indicate that IL-9 is linked to B-cell activation and autoantibody production in lupus and that IL-9 is a potential therapeutic target for SLE. MATERIALS AND METHODS MiceFemale MRL/lpr and C57BL/6 mice (3 months old) were purchased from the Shanghai Laboratory Animal Center (Chinese Academy of Sciences) and maintained under pathogen-free conditions. The animal protocol was approved by the Institutional Animal Use Committee of the Shanghai Institute for Biological Sciences. Some experiments were performed as modified methods (15,16). MRL/lpr mice were randomized into two groups containing six mice each and were treated with intraperitoneal (IP) injections of phosphate-buffered saline, anti-IL-9 antibody (100 μg/mouse), or anti-IL-19 antibody (100 μg/mouse) plus anti-IL-17 antibody (100 μg/mouse), (eBioscience, San Diego, CA, USA) once every 4 wks for 12 wks, and gremial center formation and kidney injury was analyzed. All antibodies were obtained from eBioscience. To quantify protein in the urine, we collected the total volume of urine excreted over 24 h and measured urinary protein by enzyme-linked immunosorbent assay (ELISA) (Nanjing Jianchen Bioengineering Company, Nanjing, China). Cytokine and dsDNA Antibody DetectionELISA kits were used to evaluate mouse serum levels of IL-9 (eBioscience) and anti-dsDNA anti...

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin-9 Is Associated with Elevated Anti-Double-Stranded DNA Antibodies in Lupus-Prone Mice

Yang

et al. 2015

Mol Med

View full text Add to dashboard Cite

show abstract

“…Data from Ma et al show no significant difference of IL-9 production between simple AD patients and AD patients with allergic rhinitis or asthma, and IL-9 can promote the secretion of VEGF by keratinocytes in a time-and dose-dependent manner, indicating that the pathogenesis of AD may be mediated by the increased release of VEGF by keratinocyes after IL-9 stimulation [44].…”

Section: Atopic Dermatitis (Ad)mentioning

confidence: 97%

“…Three groups have reported that IL-9 expression increases in AD patients compared with control group [4,11,44], demonstrating the essential role of IL-9 in AD, an inflammatory disorder of the skin characterized by an impaired immune response. Data from Ma et al show no significant difference of IL-9 production between simple AD patients and AD patients with allergic rhinitis or asthma, and IL-9 can promote the secretion of VEGF by keratinocytes in a time-and dose-dependent manner, indicating that the pathogenesis of AD may be mediated by the increased release of VEGF by keratinocyes after IL-9 stimulation [44].…”

Section: Atopic Dermatitis (Ad)mentioning

confidence: 99%

Differentiation, Regulation and Function of Th9 Cells

Jia

2014

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Naïve CD4(+) T cells are activated and differentiate to distinct lineages of T helper (Th) cells, which are involved in physiological and pathological processes by obtaining the potential to produce different lineage-specific cytokines that mediate adaptive immunity. In the past decade, our knowledge of Th cells has been significantly expanded with the findings of new lineages. Interleukin (IL)-9 producing T cells are recently identified. In consideration of the ability to preferentially secret IL-9, these cells are termed Th9 cells. Given the multiple function of IL-9, Th9 cells participate in the lesion of many diseases, such as allergic inflammation, tumor, and parasitosis. In this chapter, we will focus on the cytokines, co-stimulatory factors, and transcriptional signaling pathways, which regulate Th9 cells development as well as stability, plasticity, and the multiple roles of Th9 cells in vivo.

show abstract

“…Une étude récente a montré une augmentation significative du nombre de cellules Th9 dans le sang de patients atteints de dermatite atopique [19,44] (➜). Les Th9 semblent également être impliqués dans la maladie asthmatique.…”

Section: Maladies Allergiquesunclassified