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PARP inhibition by olaparib or gene knockout blocks asthma-like manifestation in mice by modulating CD4(+) T cell function.

BACKGROUND: An important portion of asthmatics do not respond to current therapies. Thus, the need for new therapeutic drugs is urgent. We have demonstrated a critical role for PARP in experimental asthma. Olaparib, a PARP inhibitor, was recently introduced in clinical trials against cancer. The objective of the present study was to examine the efficacy of olaparib in blocking established allergic airway inflammation and hyperresponsiveness similar to those observed in human asthma in animal models of the disease. METHODS: We used ovalbumin (OVA)-based mouse models of asthma and primary CD4(+

The disulfide bond between cysteine 10 and cysteine 34 is required for CCL18 activity.

Asthma is a Th2-mediated disease that involves Th2 cell and eosinophil migration into the bronchial mucosa which is dependent upon the expression of a specific set of chemokines within the lung. Among them, CCL18 seems to play a key role because of its preferential expression in the lung, and its up-regulation by Th2 cytokines. Here, we show that the optimal naïve T cell and basophil chemotaxis, and basophil histamine release induced by rhCCL18 occurred at a 100 time lower concentration with CHO-derived rhCCL18 than with E. coli-derived rhCCL18. FT-ICR mass spectrometry of the intact chemokine

[Influence of blockade of costimulation on Th1/Th2 cytokines shift in unexplained early recurrent spontaneous].

OBJECTIVE: To assess the influence of blockade of costimulation on Th1/Th2 Cytokines shift in unexplained early recurrent spontaneous abortion (URSA). METHODS: The levels of IL-2, IFN-gamma and IL-4 were determined by ELISA in the supernatant of cultured maternal peripheral blood mononuclear cells (PBMC) from 30 patients of URSA. Cytokine synthesis was induced by activation with antigens from a choriocarcinomer cell line of JEG-3, with CTLA4Ig at concentrations of 10 microg/mL and 1 microg/mL (experiment groups), or with IgG at the same concentrations (control groups). RESULTS: The CTLA4Ig g

Evaluation of the Synergistic Effects of Mineral and Postbiotics Mixtures in Ameliorating Atopic Dermatitis in the NC/Nga Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory skin condition influenced by immune dysregulation. This study aimed to evaluate the effects of a mineral-postbiotic (Lactobacillus plantarum VIOAP03 and Lactobacillus fermentum VIMPP04) mixture to alleviate AD symptoms in the NC/Nga mouse model. AD was induced in NC/Nga mice using HDM ointment throughout experiment. After inducing AD skin lesions, mice were orally administered ED mineral powder, postbiotics, and a mixture of ED mineral powder and postbiotics. Key parameters measured included dermatitis score, transepidermal water loss (TEWL), an

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease.

Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acting as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory signal, IL-33 binds to the surface receptor ST2, which enhances mast cell, Th2, regulatory T cell, and innate lymphoid cell type 2 functions. Besides these Th2 roles, free IL-33 can activate CD8+ T cells during ongoing Th1 immune responses to potentiate its cytotoxic function. Celiac Disease (CD) is a

Citrus juice fermented with Lactobacillus plantarum YIT 0132 alleviates symptoms of perennial allergic rhinitis in a double-blind, placebo-controlled trial.

This study aimed to examine whether citrus juice fermented with Lactobacillus plantarum YIT 0132 (LP0132), which was pasteurised after ferme … e LP0132 group, but not the placebo group, showed significant attenuation of type 2 helper T cells (Th2 cells)/helper T cells, serum total immunoglobulin E (IgE), and eosinophil cationic protein (ECP), and showed significant augmentation of type 1 helper T cells (Th1 cells)/Th2 cells at 8 weeks of intervention compared with baseline. It is suggested that da …

Administration of an IL-12-encoding DNA plasmid prevents the development of chronic graft-versus-host disease (GVHD).

The transfer of DBA/2 spleen cells into (C57BL/10 x DBA/2)F1 mice induces chronic graft-vs-host disease (GVHD), which is characterized by the production of Th2 cytokines, hypergammaglobulinemia, and immune complex-mediated glomerulonephritis like systemic lupus erythematosus. IL-12 strongly induces the production of Th1 cytokines and reduces Th2 activity in vivo. In this study, the effect of gene therapy on the development of murine chronic GVHD was examined using an IL-12-encoding plasmid (pCAGGSIL-12), with the expectation that it might regulate Th1/Th2 activity and have a beneficial impact

Cutaneous neuropeptides: the missing link between psychological stress and chronic inflammatory skin disease?

A "brain-skin" connection has been long been observed between chronic stress and chronic inflammatory skin disease including urticaria, psoriasis, atopic dermatitis, and prurigo nodularis. The relationship appears to be bidirectional. Chronic psychological stress has been shown to sustain hyperactivity of the sympathetic branch of the autonomic nervous system. Chronic stress is proinflammatory and in the context of several dermatologic disorders may be associated with an increase in dermal nerve fiber density, mast cells, nerve growth factor and calcitonin-gene-related peptide (CGRP). Furtherm

Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous upper airway disease with multiple etiologies. Clinically, CRSwNP can be classified into either eosinophilic or non-eosinophilic subtypes. The eosinophilic phenotype of CRSwNP is widely thought to be highly associated with recurrence of nasal polyps or surgical failure. Epithelial cells have a crucial role in the development of Th2-biased airway diseases. Recent studies have shown that a wide range of external stimuli such as allergens and microorganisms can elicit the release of epithelial-derived Th2-driving cytokines and c

Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity.

Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra-/-, Il17rb-/-, and Il17rc-/- mice failed to develop iBALT.

Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.

It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further redu

Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology.

Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious

The effect of low-temperature-induced immune activation in elderly idiopathic facial palsy: the association between Th1/Th2 imbalance and facial nerve inflammation.

The pathogenesis of idiopathic facial palsy in the elderly has not been fully elucidated. Recent studies have shown that exposure to low temperatures may participate in the pathological process through immune-mediated pathways. This article reviews that cold stimulation can disrupt the Th1/Th2 immune balance, manifested as reduced secretion of Th1-type cytokines and upregulation of Th2-type cytokines, thereby inducing peripheral inflammatory responses around the facial nerve, leading to nerve edema, demyelination, and conduction dysfunction. Due to the immune aging characteristics of the elder

Elevated antigen-specific Th2 type response is associated with the poor prognosis of hand, foot and mouth disease.

The immunopathogenesis of severe hand, foot and mouth disease (HFMD) remains elusive. This study revealed that enterovirus 71 (EV71) epitope-specific CD4+ T cell responses of HFMD patients were skewed toward a Th2 cytokine profile. Patients that demonstrated higher levels of IL-4 expression in their CD4 T cells following antigen stimulation in vitro tended to have a more prolonged period of high fevers and a longer duration of illness. Thus, an increase of EV71 epitope-specific Th2 type response may portend the poor prognosis for some HFMD patients.

WASP, Tregs, and food allergies - rare disease provides insight into a common problem.

Dysregulation of the type 2 immune system presents with various manifestations, including allergic inflammation, and has emerged as an alarming public health issue. The pathological mechanisms that underlie T helper type 2 cell-driven (Th2-driven) allergic diseases remain unclear. In particular, it is not completely understood how type 2 immunity is restricted in inflammatory responses. In this issue of the JCI, Lexmond et al. use Wiskott-Aldrich syndrome as a model disease and establish that the Wiskott-Aldrich gene product (WASP) serves an essential role in T regulatory cells to contain Th2

CRTH2 имеет решающее значение для клеток IL-1β, производящих B, во время экспериментального аутоиммунного энцефаломиелита у мышей с помощью сигнала p38.

Клетки B играют решающую роль в патогенезе аутоиммунных подстрекательских заболеваний, таких, как множественный склероз (МС). Как рецептор простагландина D2, молекула гомологового рецептора, выраженная на клетках TH2 (CRTH2), как известно, участвует в активации клеток TH2, но ее функция в B лимфоцитах не ясна. Здесь мы показываем, что CRTH2 является критическим для подмножества клеток, производящих IL-1β. Удаление мышей из клеток B-специализированного типа Crth2 свидетельствует о сокращении количества клеток IL-1β-производящих B, что приводит к улучшению экспериментального аутоиммунного энцефа

Совпадение в аннотации оригинала
B cells play a critical role in the pathogenesis of autoimmune inflammatory diseases such as multiple sclerosis (MS). As a receptor of prostaglandin D2, chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) is known to be involved in Th2 cell activation, but its function in B lymphocytes is unclear. Here, we show that CRTH2 is critical …

T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses.

During infection, the release of damage-associated molecular patterns, so-called "alarmins," orchestrates the immune response. The alarmin IL-33 plays a role in a wide range of pathologies. Upon release, IL-33 signals through its receptor ST2, which reportedly is expressed only on CD4(+) T cells of the Th2 and regulatory subsets. Here we show that Th1 effector cells also express ST2 upon differentiation in vitro and in vivo during lymphocytic choriomeningitis virus (LCMV) infection. The expression of ST2 on Th1 cells was transient, in contrast to constitutive ST2 expression on Th2 cells, and m…

Serum IL-1ra is elevated in lepromatous leprosy patients.

Patterns of production of specific cytokines are accepted as standards for T-lymphocyte subsets in diseases caused by intracellular parasites. These lymphocyte subsets (Th1 and Th2) have been associated with the different poles of the leprosy spectrum. Lepromatous leprosy (LL) onset correlates with cytokines produced by Th2 cells on the grounds of the patient's poor cellular immune response, i.e., interleukin 2 (IL-2) and gamma interferon (IFN-gamma) deficiency. On the other hand, tuberculoid leprosy (TL) has been associated with a Th1 response. Moreover, pro-inflammatory cytokines like IL-1 b…

Profiles of Th1 and Th2 cytokines after primary and secondary infection by Schistosoma mansoni in the semipermissive rat host.

In contrast to most mouse strains, rats eliminate the primary schistosome burden around 4 weeks postinfection and subsequently develop protective immunity to reinfection. In rat schistosomiasis, we have shown predominant expression of a Th2-type cytokine response at the mRNA level after primary infection. In the present study, we showed a significant increase in interleukin-4 (IL-4) mRNA expression in inguinal lymph nodes early after a secondary infection. IL-5 mRNA expression showed a significant increase at days 2 and 4 postreinfection in the spleen and lymph nodes, respectively. We did not

Group 2 Innate Lymphoid Cells in Allergic Rhinitis.

Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. … articular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive u …