- Browse by Author
Browsing by Author "Glosson-Byers, Nicole L."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item STAT4 is required for IL-23 responsiveness in Th17 memory cells and NKT cells(Taylor & Francis Group, 2014-10-30) Glosson-Byers, Nicole L.; Sehra, Sarita; Kaplan, Mark H.; Department of Pediatrics, School of MedicineSTAT4 is a critical mediator of inflammatory immunity and is required for all known IL-12 biological responses, including the induction of IFN-γ and development of Th1 cells. We demonstrate that IL-23, an IL-12-related cytokine, also requires STAT4 for optimal IL-17 secretion from memory T helper cells and NKT cells. Although IL-23 stimulation had modest effects on STAT4 activation, STAT4-deficiency results in reduced Il23r expression. These data demonstrate a restricted requirement for STAT4 in innate and adaptive IL-17-secreting T cell responses that might contribute to inflammatory immunity.Item Th17 cells demonstrate stable cytokine production in a proallergic environment(The American Association of Immunologists, 2014-09-15) Glosson-Byers, Nicole L.; Sehra, Sarita; Stritesky, Gretta L.; Yu, Qing; Awe, Olufolakemi; Pham, Duy; Bruns, Heather A.; Kaplan, Mark H.; Department of Pediatrics, IU School of MedicineTh17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and allergic inflammation. After exposure to an appropriate cytokine environment, Th17 cells can acquire a Th1-like phenotype, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we used an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F. In vitro-derived Th17 cells adopted signature cytokine and transcription factor expression when cultured under Th1-, Th2-, or Th9-polarizing conditions. In contrast, using two models of allergic airway disease, Th17 cells from the lungs of diseased mice did not adopt Th1, Th2, or Th9 effector programs, but remained stable IL-17 secretors. Although in vitro-derived Th17 cells expressed IL-4Rα, those induced in vivo during allergic airway disease did not, possibly rendering them unresponsive to IL-4-induced signals. However, in vitro-derived, Ag-specific Th17 cells transferred in vivo to OVA and aluminum hydroxide-sensitized mice also maintained IL-17 secretion and did not produce alternative cytokines upon subsequent OVA challenge. Thus, although Th17 cells can adopt new phenotypes in response to some inflammatory environments, our data suggest that in allergic inflammation, Th17 cells are comparatively stable and retain the potential to produce IL-17. This might reflect a cytokine environment that promotes Th17 stability, and allow a broader immune response at tissue barriers that are susceptible to allergic inflammation.Item Topical Prostaglandin E Analog Restores Defective Dendritic Cell–Mediated Th17 Host Defense Against Methicillin-Resistant Staphylococcus Aureus in the Skin of Diabetic Mice(American Diabetes Association, 2016-12) Dejani, Naiara N.; Brandt, Stephanie L.; Piñeros, Annie; Glosson-Byers, Nicole L.; Wang, Sue; Son, Young Min; Medeiros, Alexandra I.; Serezani, C. Henrique; Microbiology and Immunology, School of MedicinePeople with diabetes are more prone to Staphylococcus aureus skin infection than healthy individuals. Control of S. aureus infection depends on dendritic cell (DC)–induced T-helper 17 (Th17)–mediated neutrophil recruitment and bacterial clearance. DC ingestion of infected apoptotic cells (IACs) drive prostaglandin E2 (PGE2) secretion to generate Th17 cells. We speculated that hyperglycemia inhibits skin DC migration to the lymph nodes and impairs the Th17 differentiation that accounts for poor skin host defense in diabetic mice. Diabetic mice showed increased skin lesion size and bacterial load and decreased PGE2 secretion and Th17 cells compared with nondiabetic mice after methicillin-resistant S. aureus (MRSA) infection. Bone marrow–derived DCs (BMDCs) cultured in high glucose (25 mmol/L) exhibited decreased Ptges mRNA expression, PGE2 production, lower CCR7-dependent DC migration, and diminished maturation after recognition of MRSA-IACs than BMDCs cultured in low glucose (5 mmol/L). Similar events were observed in DCs from diabetic mice infected with MRSA. Topical treatment of diabetic mice with the PGE analog misoprostol improved host defense against MRSA skin infection by restoring DC migration to draining lymph nodes, Th17 differentiation, and increased antimicrobial peptide expression. These findings identify a novel mechanism involved in poor skin host defense in diabetes and propose a targeted strategy to restore skin host defense in diabetes.