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    Circulating Th1, Th2, Th9, Th17, Th22, and Treg Levels in Aortic Dissection Patients. Ye Jing,Wang Yuan,Wang Zhen,Ji Qingwei,Huang Ying,Zeng Tao,Hu Haiying,Ye Di,Wan Jun,Lin Yingzhong Mediators of inflammation Background:Previous studies demonstrated that the subsets of CD4+ T helper (Th) cells are closely related to vascular diseases, including atherosclerosis and hypertension. This study is aimed at investigating the circulating Th1, Th2, Th9, Th17, Th22, and Treg levels in aortic dissection (AD) patients. Methods:Blood samples from AD ( = 56) and non-AD (NAD, = 24) patients were collected, and the circulating levels of Th1, Th2, Th9, Th17, Th22, and Treg cells and their transcription factors and functional cytokines were measured by flow cytometric analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays, respectively. In addition, the human aortic vascular smooth muscle cells (HASMCs) were treated with saline, angiotensin II (Ang II), or plasma from AD patients. Results:Compared with the levels in the NAD group, the Th1, Th9, Th17, Th22, and their transcription factor levels were increased and the Th2, Treg, and their transcription factor levels exhibited a decreasing trend in AD patients. In addition, higher IFN-, IL-9, IL-17, and IL-22 levels and lower IL-4 and IL-35 levels were observed in AD patients. Simple linear regression analysis and binary logistic regression analysis suggested that Th1/IFN-, IL-9, Th17/IL-17, and Th22/IL-22 positively regulated the occurrence of AD, while Th2/IL-4 and Treg/IL-35 negatively regulated the occurrence of AD. Plasma from AD patients further increased Bax mRNA levels but decreased Bcl2 and -SMA mRNA levels in Ang II-treated HASMCs. Conclusions:Changes in Th1, Th2, Th9, Th17, Th22, and Treg activity are associated with the onset of AD. Different subsets of CD4+ T cells play different roles in the presence of AD. 10.1155/2018/5697149
    [Determination of Th9 cells and IL-9 in children with Mycoplasma pneumoniae infection]. Wang Jian-Yong,Zheng Jing,Xing Hai-Yan,Jia Xiu-Hong Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To investigate the clinical significance of T helper type 9 (Th9) cells and interleukin-9 (IL-9) in children suffering from Mycoplasma pneumoniae (MP) infection. METHODS:A total of 86 children who were diagnosed with MP infection between January 2013 and June 2014 were classified into upper respiratory infection (URI) group (n=29), mild MP pneumonia (MPP) group (n=32) and severe MPP group (n=25). Twenty-eight healthy children were used as the control group. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, and the percentage of Th9 cells in peripheral blood was measured by flow cytometry. Serum IL-9 level was determined using ELISA. RESULTS:The URI, mild MPP, and severe MPP groups had significantly higher percentages of Th9 cells and IL-9 levels than the control group (P<0.05); the mild MPP and severe MPP groups had significantly higher percentages of Th9 cells and IL-9 levels than the URI group (P<0.05), and the two indices were significantly higher in the severe MPP group than in the mild MPP group (P<0.01). CONCLUSIONS:Children with MP infection have an elevated percentage of Th9 cells and IL-9 expression, both of which are positively correlated with the severity of the disease. It can be predicted that Th9 cells and IL-9 can be used as evaluation indicators for the progression and outcome of children with MP infection.
    Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. Ciccia Francesco,Guggino Giuliana,Rizzo Aroldo,Manzo Antonio,Vitolo Barbara,La Manna Marco Pio,Giardina Giuseppina,Sireci Guido,Dieli Francesco,Montecucco Carlo Maurizio,Alessandro Riccardo,Triolo Giovanni Rheumatology (Oxford, England) OBJECTIVE:IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients. METHODS:IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides. RESULTS:IL-9 was overexpressed in RA synovial tissues and correlated with the degree of histological organization of B and T cells in ectopic lymphoid structures. The majority of IL-9-producing cells were identified as CD3(+) cells. Increased mRNA and protein expression of IL-9R, IL-4, TSLP and TGF-β was also observed in RA synovial tissue. Blood peripheral Th9 cells were expanded by citrullinated peptides. CONCLUSION:These results indicate that Th9 cells and IL-9 were frequently detected in peripheral blood mononuclear cells and synovia of RA patients. A possible pathogenic role for Th9 in RA is discussed. 10.1093/rheumatology/kev252
    Th9 cells in the pathogenesis of EAE and multiple sclerosis. Elyaman Wassim,Khoury Samia J Seminars in immunopathology Interleukin (IL)-9 producing CD4 T helper cells (Th9) are the newest addition to the T helper cell subsets. IL-9 binds to a heterodimeric receptor consisting of the IL-9 receptor (IL-9R) and a common γ chain also presents in IL-2, IL-4, IL-7, and IL-15 receptor complexes. In addition to Th9 cells, Th17 cells secrete smaller amounts of IL-9. Many functional and regulatory roles associated with Th9 cells are currently not fully understood. IL-9 is a pleiotropic cytokine that affects the activity of multiple cell types in the immune compartment as well as in the central nervous system (CNS). Initially implicated in type 2 inflammation, IL-9 has been recently shown to be a key player in regulating autoimmune responses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Here, we review the current understanding of the role of Th9/IL-9 signaling in EAE and MS. We summarize the source and regulation of Th9 cells in vivo, the influence of IL-9 signaling on peripheral and CNS-resident cells in EAE, and the association between IL-9 and MS disease activity. 10.1007/s00281-016-0604-y
    Th9 Cells: New Member of T Helper Cell Family. Goswami Ritobrata Methods in molecular biology (Clifton, N.J.) T Helper cells (CD4+ T cells) constitute one of the key arms of adaptive immune responses. Differentiation of naïve CD4+ T cells into multiple subsets ensure a proper protection against multitude of pathogens in immunosufficient individual. After differentiation, T helper cells secrete specific cytokines that are critical to provide immunity against various pathogens. The recently discovered Th9 cells secrete the pleiotropic cytokine, IL-9. Although IL-9 was cloned more than 25 years ago and characterized as a Th2 cell-specific cytokine, not many studies were carried out to define the function of IL-9. This cytokine has been demonstrated to act on multiple cell types as a growth factor. After the discovery of Th9 cells as an abundant source of IL-9, renewed focus has been generated. In this chapter, I discuss the biology and development of IL-9-secreting Th9 cells. Furthermore, I highlight the role of Th9 cells and IL-9 in health and diseases. 10.1007/978-1-4939-6877-0_1
    T9 cells in skin disorders. Clark Rachael A,Schlapbach Christoph Seminars in immunopathology Interleukin 9 secreting T9 cells have been proposed as the latest addition to the family of T helper cell subsets. While a growing body of evidence from animal models points to important roles for these cells in allergic inflammation of the lung, autoinflammation of the gastrointestinal tract, and tumor immunity, their role in skin immunity and skin immunopathology remains poorly defined. Interestingly, studies of T helper cells from healthy humans suggest that T9 cells are predominantly skin-homing and skin-resident and that they are involved in protection against extracellular pathogens. Thus, T9 cells have entered the stage as potential mediators of cutaneous pathology. However, under which conditions and by which mechanisms these cells contribute to skin immunity and disease still has to be investigated. Here, we review our current understanding of T9 cells as skin-tropic T helper cells and their involvement in skin pathology. Further, we discuss open questions with regard to the intricate nature of interleukin 9 producing T helper cells. 10.1007/s00281-016-0607-8
    Th9 and Th22 immune response in young patients with type 1 diabetes. Ryba-Stanisławowska Monika,Werner Paulina,Brandt Agnieszka,Myśliwiec Małgorzata,Myśliwska Jolanta Immunologic research Th17, Th22 and Th9 are recently discovered effector populations that may contribute to the pathogenesis of autoimmune and inflammatory diseases. The presented study aimed to investigate the link between Th22 and Th9 subsets in type 1 diabetes, as this disease involves different subsets of CD4+ T lymphocytes. The study groups consisted of 23 patients with type 1 diabetes and 11 healthy individuals. All subjects had CD4+IL-22 Th22 and CD4+IL-9 Th9 lymphocytes investigated by flow cytometry. In addition, the plasma concentrations of IL-22 as well as IL-9 were analyzed. Our study demonstrated that Th9 and Th22 cell counts as well as their plasma cytokines were upregulated in patients with type 1 and correlated with HbA1c and CRP values. Taking these all into account, one can conclude that Th22 and Th9 lymphocyte activities may contribute to chronic, low-level inflammation that is considered an integral part of type 1 diabetes. 10.1007/s12026-015-8765-7
    Th9 Cells as a New Player in Inflammatory Skin Disorders. Jadali Zohreh Iranian journal of allergy, asthma, and immunology CD4+T cells are composed of different subpopulations that differ in developmental pathways, surface markers, and their products. Among the catalog of these cells is Th9 cell subset that has a great capacity of Interleukin (IL)-9 production. They could be involved in the pathogenic or protective immune responses. Therefore, it is important to know how Th9 cells and cytokines influence the function of the human immune system as multitasking machinery, both in isolation or after the interaction with other surrounding cells. Since an important characteristic of Th9 cells is their tropism for skin, this article reviews the physiological and pathophysiological functions of Th9 and its cytokines under normal conditions and inflammatory skin disorders.
    Flow Cytometric Assessment of STAT Molecules in Th9 Cells. Garo Lucien P,Beynon Vanessa,Murugaiyan Gopal Methods in molecular biology (Clifton, N.J.) IL-9-producing Th9 cells are a novel subset of T helper cells that develop independently of other T helper subsets. Th9 cells have been implicated in the pathogenesis of allergic asthma and autoimmunity, while also serving as critical effector T cells in mediating antitumor immune responses. Concomitant presence of TGF-β and IL-4 lead to the differentiation of naïve CD4 T cells towards the Th9 phenotype. In addition, several cytokines, including IL-1β, IL-2, IL-25, and IL-33, further amplify Th9 responses. Negative regulators of Th9 cells include other cytokines such as IFN-γ, IL-23, and IL-27. Here, we describe a detailed protocol for the analysis of STAT molecules involved in the differentiation of Th9 cells and Th9 inhibition by IL-27. 10.1007/978-1-4939-6877-0_10
    IL-9 and Th9 Cells in Tumor Immunity. He Ying,Dong Lin,Cao Yejin,Bi Yujing,Liu Guangwei Advances in experimental medicine and biology T cells can be categorized into functionally diverse subpopulations, which include Th1, Th2, Th9, Th17, Th22, and Tfh cells and Foxp3 Tregs, based on their role in maintaining normal immune homeostasis and affecting pathological immune-associated diseases. Among these subpopulations, Th9 cells are relatively new, and less is known about their signaling and effects on tumor immunity. Recently, some studies have focused on regulation of the IL-9/IL-9R signaling pathway and Th9 cell differentiation and their roles in tumor environments. Herein, we summarize recent progress in understanding the regulatory signaling of IL-9 and Th9 cells and their critical roles and mechanisms in antitumor immunity. 10.1007/978-3-030-38315-2_3
    Th9 Cells in Peripheral Blood Increased in Patients with Immune-Related Pancytopenia. Shao Qing,Wang Yangyang,Liu Zhaoyun,Liu Hui,Wang Yihao,Zhao Yang,Li Lijuan,Fu Rong Journal of immunology research Background:Immune-related pancytopenia (IRP) is a kind of autoimmune disease mediated by autoantibodies in bone marrow. T helper 9 (Th9) cell is a new subset of T cell discovered recently, which mainly expresses cytokine interleukin-9 (IL-9) to exert immune function. Th9 cells are associated with a variety of inflammatory diseases, but the role of Th9 cells in IRP remains unclear. Methods:Fifty patients with IRP and 20 healthy controls were enrolled. The percentage of Th9 cells was detected by flow cytometry (FCM) and ELISA. CD4 lymphocytes were sorted by magnetic beads, and the mRNA expression levels of Th9 cells related transcription factors PU.1 and BATF were detected by RT-PCR. Results:The percentage of Th9 cells in CD3CD4 cells was 2.73 ± 1.96% in the untreated group, which was significantly higher than those in the remission group (1.21 ± 0.86%) ( < 0.01) and the control group (0.68 ± 0.40%) ( < 0.001). And that in the remission group was significantly higher than that in the control group ( < 0.05). The level of IL-9 in the untreated group was 183.91 ± 112.42 pg/mL, which was significantly higher than that in the remission group (105.96 ± 64.79 pg/mL) ( < 0.01) and control group (56.03 ± 14.49 pg/mL) ( < 0.001). That in the remission group was also significantly higher than that in the control group ( < 0.01). They were negatively correlated with hemoglobin, red blood cell, white blood cell, and platelet counts and positively correlated with the percentage of CD19B cells and CD5CD19/CD19B cells, respectively. The mRNA expression levels of PU.1 and BATF in IRP patients were higher than those in controls ( < 0.05). Conclusions:The percentage of Th9 cells in the peripheral blood and the level of IL-9 in the serum of patients with IRP were increased, which was related to the severity of the disease. 10.1155/2020/6503539
    Th9 Cells in Allergic Disease. Angkasekwinai Pornpimon Current allergy and asthma reports PURPOSES OF REVIEW:Th9 cells are recognized as a novel subset of effector T helper cells that preferentially produce IL-9. Here, we provide a current update on the reports related to the function of Th9 cells in allergic inflammatory diseases. RECENT FINDINGS:The effector Th9 cells differentiating from naïve T helper cells have recently been identified. Because of accumulating findings of Th9 cells in many inflammatory diseases, including allergic diseases, diverse functions of Th9 cells in regulating immune responses have been suggested. Related reports indicate multiple sources of IL-9 besides Th9 cells and their association with the pathogenesis of allergic rhinitis, asthma, atopic dermatitis, contact dermatitis, and food allergy. More recently, elements of the epigenetic landscape involving in the regulation of IL-9 by Th9 cells have been identified to be the potential target for allergic inflammation. This review provides the most recent information about Th9 cells and their contribution in airway allergic disease, skin, and food allergy. 10.1007/s11882-019-0860-8
    Changes in the Th9 cell population and related cytokines in the peripheral blood of infants with recurrent wheezing. Liu Guangliang,Qian Lei,Xu Tonghui,Yu Jianxiu,Li Ming,Cui Yubao Central-European journal of immunology Introduction:T helper type 9 (Th9) cells have been shown to play a key role in initiating allergic reactions and promoting airway inflammation. However, to the best of our knowledge, their role has not been analyzed in infants with recurrent wheezing. Material and methods:We performed a case-control study including 34 infants with recurrent wheezing and the same number of healthy infants as controls; all subjects were aged 1- to 3-years-old. The Th9 cell populations in the peripheral blood of these subjects were analyzed using flow cytometry, along with the assessment of Th9- and Th2-related plasma cytokine levels, including interleukin (IL)-1β, IL-4, IL-5, IL-9, IL-10, IL-13, IL-17A, and IL-33, and transforming growth factor β1 (TGF-β1) using a Luminex 200 immunoassay. Results:Our results indicatedthat infants with recurrent wheezing had higher percentages of Th9 cells (median, 0.69%; range, 0.46-1.08%) as compared to healthy infants (median, 0.25%, range, 0.13-0.36%; p < 0.05). In addition, infants with recurrent wheezing also exhibited higher plasma levels of cytokines IL-4, IL-9, IL-10, IL-33, and TGF-β1. Furthermore, the percentage of Th9 cells was positively correlated with the levels of IL-4 (r = 0.408, p < 0.05) and IL-9 (r = 0.644, p < 0.05) in the peripheral blood of wheezing infants. Conclusions:Our findings suggest that the percentage of Th9 cells is increased in infants with recurrent wheezing; thus, Th9 cells may play an important role in the pathogenesis of recurrent wheezing. 10.5114/ceji.2020.94683