Several pathophysiologic features of allergic inflammation, such as T(H) differentiation, the regulation of IgE, eosinophilia, mast cell proliferation, and cellular recruitment, are regulated by various cytokines. It has been of particular interest to investigate the underlying mechanism in the preferential activation of T(H2) cells by allergens. Although interleukin (IL)-4 is the major determinant of T(H2) differentiation, the original cellular source of IL-4 and the nature of the interaction between IL-4 and TH2 differentiation remain unclear. Recent studies have demonstrated that the regulation of IgE depends primarily on the functional activities of IL-4, IL-13, and IFN-gamma. Eosinophilia and an increased number of mast cells characterize allergic inflammation, which is a T cell-dependent process. IL-5 is the major chemotactic and activating factor of eosinophils. Mast cell proliferation results from several cytokines, including IL-3, IL-9, and IL-10. It has been suggested that, in the late phase reaction of allergic inflammation, proinflammatory cytokines released from mast cells, eosinophils, and T(H2) cells enhance the expression of adhesion molecules and chemokines that further promote the allergic cellular milieu.
Allergens ; Chemokines ; Cytokines* ; Eosinophilia ; Eosinophils ; Hypersensitivity* ; Immunoglobulin E ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-9 ; Interleukins ; Mast Cells

Several pathophysiologic features of allergic inflammation, such as T(H) differentiation, the regulation of IgE, eosinophilia, mast cell proliferation, and cellular recruitment, are regulated by various cytokines. It has been of particular interest to investigate the underlying mechanism in the preferential activation of T(H2) cells by allergens. Although interleukin (IL)-4 is the major determinant of T(H2) differentiation, the original cellular source of IL-4 and the nature of the interaction between IL-4 and TH2 differentiation remain unclear. Recent studies have demonstrated that the regulation of IgE depends primarily on the functional activities of IL-4, IL-13, and IFN-gamma. Eosinophilia and an increased number of mast cells characterize allergic inflammation, which is a T cell-dependent process. IL-5 is the major chemotactic and activating factor of eosinophils. Mast cell proliferation results from several cytokines, including IL-3, IL-9, and IL-10. It has been suggested that, in the late phase reaction of allergic inflammation, proinflammatory cytokines released from mast cells, eosinophils, and T(H2) cells enhance the expression of adhesion molecules and chemokines that further promote the allergic cellular milieu.
Allergens ; Chemokines ; Cytokines* ; Eosinophilia ; Eosinophils ; Hypersensitivity* ; Immunoglobulin E ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-9 ; Interleukins ; Mast Cells

Group 2 innate lymphoid cells (ILC2s) are the "mirror cells" of Th2 cells. Although the total cell number of ILC2s is far less than that of CD4⁺ Th2 cells in the body, the activated ILC2s have a more powerful biological activity than CD4⁺ Th2 cells and can rapidly enhanced Th2-cell inflammatory reaction. It plays an important role in the pathogenesis of allergic respiratory diseases. The transmitters that activate ILC2s include inflammatory cytokines (IL-33, IL-25, TSLP, IL-4, IL-9), lipid transmitters (prostaglandins, leukotrienes), and other activating transmitters (ICOS, Complement C3a, neuropeptide receptor, vasoactive intestinal peptide and calcitonin gene-related peptide, etc). Activated ILC2s produce large amounts of IL-4, IL-5, IL-9, IL-13, and amphiregulin and other inflammatory mediators, and induce airway hyperresponsiveness, mucus secretion and airway remodeling and other respiratory allergic reactions. Therefore, respiratory allergic diseases, especially steroid-dependent asthma, could be treated potentially by inhibiting the activation of ILC2s. Hereby, we summarized the immunobiology of ILC2s, the initiation of ILC2s in allergic inflammation, the relationship between ILC2s and respiratory allergic diseases, and the recent advances in biological agents targeted by ILC2s.
Humans ; Immunity, Innate ; Interleukin-4 ; Interleukin-9 ; Lymphocytes ; Hypersensitivity ; Cytokines ; Respiratory Tract Diseases ; Inflammation

OBJECTIVE: To investigate the cytokine/chemokine profile in patients with Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH), and assess the prognostic value of survival. METHODS: Serum levels of thirty-eight cytokines/chemokines were measured by multiple cytokine assay kit in EBV-related HLH patients, EBV-infected patients, and controls. The expression profile of cytokines/chemokines was compared among groups. The changes of cytokine/chemokine expression in active and remission stage of EBV-related HLH patients were also compared, and the prognostic values for survival were evaluated. RESULTS: Serum levels of interferon-α2 (IFN-α2), interleukin (IL)-6, and IL-7 in EBV-related HLH patients were 33.67(23.23-68.78) pg/ml, (74.95±25.53) pg/ml, and 35.35(19.50-63.55) pg/ml, respectively, which were significantly higher than those in EBV-infected patients［IFN-α2: 16.07(9.87-29.63); IL-6: 55.91±20.29; IL-7: 20.40(13.35-31.40)］ and controls ［IFN-α2: 11.02(4.67-21.25); IL-6:42.64±13.41; IL-7: 16.95(14.95-33.78)］(all P<0.05). Serum levels of IL-8, IL-9, and marcophage-derived chemokine (MDC) in EBV-related HLH patients were 11.00(7.50-15.27) pg/ml, 81.30(40.79-111.0) pg/ml, and (512.6±128.7) pg/ml, respectively, which were significantly higher than those in controls ［IL-8: 6.80(5.56-8.38); IL-9: 41.30(29.82-67.91); MDC: 384.1±156.6］(all P<0.05), but there was no remarkable differences compared with EBV-infected patients (P>0.05). Serum IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC in survival and death groups of EBV-related HLH patients were analyzed by receiver operating characteristic curve with area under curve of 0.781, 0.778, 0.633, 0.805, 0.562, and 0.657, respectively (P=0.019, 0.021, 0.269, 0.015, 0.607, and 0.190). IFN-α2, IL-6, and IL-8 had good predictive effect on survival. Serum level of IFN-α2, IL-6, and MDC of EBV-related HLH patients in remission stage were significantly lower than those in active stage (P<0.05), while IL-7, IL-8, and IL-9 were not different (P>0.05). CONCLUSION IFN-α2, IL-6, IL-7, IL-8, IL-9, and MDC may take part in the pathogenesis of EBV-related HLH.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Herpesvirus 4, Human ; Cytokines/metabolism* ; Epstein-Barr Virus Infections/complications* ; Interleukin-6 ; Clinical Relevance ; Interleukin-7 ; Interleukin-8 ; Interleukin-9 ; Chemokines ; Interferons

OBJECTIVETo investigate the role of mast cells and interleukin-9 (IL-9) in B-cell non-Hodgkin lymphoma (B-NHL) development and its clinical significance.

METHODSThe expression level of CD117 in tumor tissues of 32 B-NHL patients was determined by Western blot. The infiltration of CD117⁺ mast cells (MCs) in human B-NHL tumor tissues was observed by immunohistochemistry staining. To evaluate the correlations between the data from CD117⁺ MCs and biological markers of human B-NHL, a Spearman correlation coefficient (rs) was calculated. IL-9 levels in sera of B-NHL patients were measured by ELISA. Effects of IL-9 on expressions of functional genes of mouse bone marrow-derived mast cells (BMMCs) were detected by real-time quantitative RT-PCR.

RESULTSThe expression of CD117 was upregulated significantly in human B-cell NHL involved tissues when compared with that of controls (0.0551±0.0064 vs 0.0192±0.0072, P<0.01). Infiltration of more CD117⁺ MCs was found in tissues from B-cell NHL subjects compared with that of controls. IL-9 level in serum samples from patients with B-cell NHL was higher than that from healthy controls. Addition of rIL-9 to the culture gave rise to increase in the purity of mouse BMMCs in the first three weeks. In vitro culture experiments showed that the addition of IL-9 could induce the differentiation of mouse BMMC and the expressions of MC-related genes, including CD117, Fcer1α, Mcpt1 and Mcpt5.

CONCLUSIONOur study showed that IL-9 promoted immune response mediated by MCs, and probably played important roles in B-NHL growth. Pharmacological or targeted inhibition of mast cells or IL-9 activity may provide new strategy for B-cell NHL therapy.

Animals ; Cells, Cultured ; Humans ; Interleukin-9 ; blood ; Lymphoma, B-Cell ; pathology ; Male ; Mast Cells ; immunology ; Mice

PURPOSE: Variations in barrier- or immune response-related genes are closely related to the development of atopic dermatitis (AD). This study was designed to identify genetic variations and clinical features to predict ‘recalcitrant AD.’ METHODS: AD patients were classified as treatable and recalcitrant. Treatable AD patients showed satisfactory clinical improvement with basic and topical treatments. Recalcitrant AD patients used systemic immune-suppressants for over 4 weeks as they had not shown clinical improvement with basic and topical treatments. The frequency of gene variations in barrier- (FLG 3321delA, FLG K4022X, KLK7, SPINK 1156, SPINK 1188, SPINK 2475) and immune response- (DEFB1, KDR, IL-5RA, IL-9, and IL-12RB1a, b) related genes were compared between each AD group and the controls. RESULTS: Of all, 249 treatable AD and 32 recalcitrant AD were identified. Heterozygous mutations (Hetero) in KLK7 was more frequent in recalcitrant AD patients than treatable AD, without statistical significance. Hetero in DEFB1 was more frequent in treatable AD patients. However, no other significant genetic differences between treatable and recalcitrant AD was observed. Instead, higher initial Eczema Area Severity Index (EASI) score, serum immunoglobulin E (IgE) level, allergen specific IgE for house dust mites, and family history of atopic diseases were associated with recalcitrant AD with statistical significance. CONCLUSIONS: According to our study, no genetic variation to predict recalcitrant AD was identified, suggesting that clinical manifestation, rather than genetic variations of AD patients is more likely to be an important factor in predicting the prognosis of AD. Further large-scale studies on the correlation between genetic variation and recalcitrant AD are needed.
Dermatitis, Atopic* ; Eczema ; Genetic Variation* ; Humans ; Immunoglobulin E ; Immunoglobulins ; Interleukin-9 ; Polymorphism, Single Nucleotide ; Prognosis ; Pyroglyphidae

Helper T cell (Th) has been identified as a critical immune cell for regulating immune response since 1980s. The type 2 helper Tcell (Th2), characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, plays a critical role in immune response against helminths invading cutaneous or mucosal sites. It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea. Currently, most studies have shed light on Th2 cell function and behavior in specific diseases, such as asthma and helminthes inflammation, but not on Th2 cell itself and its differentiation. Based on different cytokines and specific behavior in recent research, Th2 cell is also regarded as new subtypes of T cell, such as IL-9 secreting T cell (Th9) and CXCR5(+) T follicular helper cells. Here, we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.
Animals ; Asthma ; immunology ; metabolism ; Cell Differentiation ; physiology ; Humans ; Interleukin-9 ; metabolism ; Th2 Cells ; cytology ; immunology ; metabolism

Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens. These include IL-9 producing mucosal mast cells (MMC9s) and type 2 innate lymphoid cells (ILC2s). The involvement of these cell types in potentiating the type 2 immune response and developing the anaphylactic response to food allergens will be discussed. In addition, it has become apparent that there is a collaboration between these cells that contributes to an individual's susceptibility to IgE-mediated food allergy.
Allergens ; Cooperative Behavior ; Food Hypersensitivity* ; Gastrointestinal Tract ; Hypersensitivity ; Immune System ; Immunoglobulin E ; Interleukin-9* ; Lymphocytes* ; Mast Cells* ; Prevalence

BACKGROUND: A difference of the interleukin-18 (IL-18) mRNA expression among several proinflammatory genes was previously observed between large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and small plaque (SP) psoriasis patients (1~2 cm lesions are typical). Therefore, it is necessary to test whether there is any difference in the expression of the genes that activate IL-18 or the expression of genes that are induced by IL-18. OBJECTIVE: To test the differential mRNA expressions of caspase-1, STAT-6, MMP-1, MMP-2, MMP-9 and TIMP-1 according to the clinical types of psoriasis vulgaris lesions in Korean patients, we have analyzed the skin samples of psoriasis vulgaris patients. METHODS: The total cellular RNA of skin samples from groups of patient with LP and SP psoriasis was analyzed by performing real-time PCR (the Taqman method) to compare the differences in the mRNA expressions. RESULTS: The caspase-1 and STAT-6 mRNA expression levels from the SP lesional skin of the patients were increased compared with the caspase-1 and STAT-6 mRNA expression levels from SP non-lesional skin or normal skin, but these expression levels from the SP non-lesional skin were not significantly different from those of the LP non-lesional skin. Among MMP-1, MMP-2, MMP-9 and TIMP-1, the expressions of MMP-1, MMP-2 and MMP-9 mRNA were increased in the SP lesional skin compared with those of the SP non-lesional skin. The MMP-1 mRNA expressions in both the LP and SP lesional skin were increased compared with those in the normal skin (p=0.028 and p=0.007 respectively). The MMP-9 mRNA expression in the LP non-lesional skin was elevated compared with the MMP-9 mRNA expression in the SP non-lesional skin (p=0.047). The TIMP-1 mRNA expression levels from the non-lesional skin and the lesional skin of the psoriasis patients and the normal skin samples were not significantly different. CONCLUSION: The increased expression of MMP-9 mRNA in the LP non-lesional skin compared to that of the SP non-lesional skin in the psoriatic skin suggests that the increased MMP-9 mRNA expression is related to the large size type of lesion.
Humans ; Interleukin-18 ; Matrix Metalloproteinase 9 ; Psoriasis ; Real-Time Polymerase Chain Reaction ; RNA ; RNA, Messenger ; Skin ; Tissue Inhibitor of Metalloproteinase-1

OBJECTIVETo investigate the clinical significance of T helper type 9 (Th9) cells and interleukin-9 (IL-9) in children suffering from Mycoplasma pneumoniae (MP) infection.

METHODSA 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.

RESULTSThe 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).

CONCLUSIONSChildren 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.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Interleukin-9 ; blood ; Male ; Pneumonia, Mycoplasma ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology