TSLP drives acute T2-cell differentiation in lungs.

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is important for the development of type 2 inflammatory responses at mucosal surfaces.

Objective: In humans, TSLP level has been found to be elevated in the lungs of patients with asthma, and in mouse models, TSLP can promote type 2 airway inflammation, primarily through the activation of dendritic cells. However, the mechanisms underlying its role remain unclear.

Imbalance of Ly-6C and Ly-6C Monocytes/Macrophages Worsens Hyperoxia-Induced Lung Injury and Is Rescued by IFN-γ.

Inflammation in response to oxygen exposure is a major contributing factor in neonatal lung injury leading to bronchopulmonary dysplasia. Although increased levels of proinflammatory cytokines are seen in airway samples and blood from bronchopulmonary dysplasia patients, the innate immune responses in this common neonatal lung condition have not been well characterized. We previously reported that depletion of murine CD11b-expressing mononuclear phagocytes at birth led to severe acute hyperoxia-induced lung injury (HILI) and significant mortality.

KAP1 Regulates Regulatory T Cell Function and Proliferation in Both Foxp3-Dependent and -Independent Manners.

Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear.

Direct control of regulatory T cells by keratinocytes.

Environmental challenges to epithelial cells trigger gene expression changes that elicit context-appropriate immune responses. We found that the chromatin remodeler Mi-2β controls epidermal homeostasis by regulating the genes involved in keratinocyte and immune-cell activation to maintain an inactive state. Mi-2β depletion resulted in rapid deployment of both a pro-inflammatory and an immunosuppressive response in the skin.

Conditioning of naive CD4(+) T cells for enhanced peripheral Foxp3 induction by nonspecific bystander inflammation.

Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation.

IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis.

IL-22 plays an important role in mucosal epithelial cell homeostasis. Using a dextran sodium sulfate-induced mouse model of acute colitis, we observed an IL-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection.

MMP induced by Gr-1+ cells are crucial for recruitment of Th cells into the airways.

Th2 lymphocytes deliver essential signals for induction of asthmatic airway inflammation. We previously found that airway antigen challenge induces recruitment of Gr-1(+) neutrophils prior to the recruitment of Th2 cells. We examined, therefore, whether Gr-1(+) cells contribute to the development of Th2-dependent airway inflammation.

Epitope mapping of Mycoplasma hyopneumoniae using phage displayed peptide libraries and the immune responses of the selected phagotopes.

Phage display techniques have been widely employed to map the epitope structures which served as the basis for developing molecular vaccines. In the present study, we applied this technique to map the epitopes of Mycoplasma hyopneumoniae, the etiologic agent causing swine enzootic pneumonia, and evaluated directly the immune responses in mice of the selected phage-displayed epitopes (phagotopes). Two phage-displayed random peptide libraries were biopanned with the protein A-purified IgG of the rabbit anti-M.

Doxycycline- and tetracycline-regulated transcriptional silencer enhance the expression level and transactivating performance of rtTA.

Background: The tetracycline-regulated transcriptional silencer (tTS) has been demonstrated to mitigate leaky expression of the tetracycline-inducible promoter under uninduced condition, and, when conjugated with reverse-type tetracycline-controlled transactivator (rtTA), shows great promise for gene therapy. This effect was attributed to the effectiveness of tTS as a repressor of transcription at the tetracycline-regulated promoter. However, we observed an unexpected increase in transactivational activity by rtTA in the presence of tTS under inducible condition.

An ecdysone and tetracycline dual regulatory expression system for studies on Rac1 small GTPase-mediated signaling.

Regulated expression systems are invaluable for studying gene function, offer advantages of dosage-dependent and temporally defined gene expression, and limit possible clonal variation when toxic or pleiotropic genes are overexpressed. Previously, establishment of inducible expression systems, such as tetracycline- and ecdysone-inducible systems, required assessment of the inducible characteristics of individual clones by tedious luciferase assays. Taking advantage of a green fluorescent protein (GFP) reporter controlled by tetracycline- or ecdysone-responsive element and fluorescence-activated cell sorting, we propose a simple and efficient strategy to select highly inducible cell lines according to their fluorescence profiles after transiently transfecting the candidate cell pools with a surrogate GFP reporter.