Hypersensitivity Response to Aspergillus fumigatus: Immunopathogenesis of Allergic Airway Disease and Pulmonary Arterial Remodeling.

Sensitization of CD4+ T cells to innocuous antigens results in adverse hypersensitivity responses upon re-exposure to the antigens. In the lung, chronic hypersensitivity responses to inhaled antigens result in the immunopathogenesis of various diseases. The ubiquitous fungus Aspergillus fumigatus releases airborne conidia and is associated with several pulmonary hypersensitivity diseases. We hypothesized that repeated inhalation of A. fumigatus conidia will result in a CD4+ T cell-mediated hypersensitivity response that promotes pathological alterations in lung structure and function. Viable A. fumigatus conidia (2×106) were administered to C57BL/6 mice via the intranasal route every week for a variable number of total exposures. In a CD4+ T cell-independent manner, the innate immune response prevented growth of inhaled conidia. In a CD4+ T cell-dependent manner, a significant increase in airway lymphocytes and eosinophils resulted from several exposures to conidia. Thus, repeated inhalation of conidia resulted in a CD4+ T cell-mediated hypersensitivity response out of proportion to the fungal burden. The chronic hypersensitivity response to A. fumigatus did not result in progressive airway remodeling but did result in severe, progressive remodeling of pulmonary arteries reminiscent of the primary abnormality found in patients with pulmonary arterial hypertension. The lumens of small-to-medium sized pulmonary arteries were significantly narrowed, and the remodeled arterial walls were muscularized, fibrotic, and exhibited signs of neointimal formation. CD4+ T cells were required for the full manifestation of pulmonary inflammation and arterial remodeling, but some degree of CD4+ T cell-independent luminal narrowing was noted. Arterial remodeling developed in mice deficient for IFNγ, the critical TH1 effector cytokine, but not in mice deficient for IL-4, a critical cytokine for the manifestation of TH2 responses. IL-10-deficient mice did not develop CD4+ TH2 cells, airway eosinophilia, or arterial remodeling. Based on results from the study of IL-5-deficient mice, the TH2-mediated pathogenesis of arterial remodeling did not require eosinophils. Though mice developed severe arterial muscularization, arterial fibrosis, and significant luminal narrowing, mice did not develop pulmonary hypertension as a result. Along with several recent reports, these data support a novel mechanism for the pathogenesis of pulmonary arterial remodeling.Ph.D.ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/75857/1/shreiner_1.pd

Co-evolution of TH1, TH2 and TH17 Responses During Repeated Pulmonary Exposure to Aspergillus fumigatus Conidia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89973/1/white-coevolution_th1_th2.pd

Optically controllable magnetism in atomically thin semiconductors

We report evidence that ferromagnetic order in electrostatically doped, monolayer transition metal dichalcogenide (TMD) semiconductors can be stabilized and controlled at zero magnetic field by local optical pumping. We use circular dichroism (CD) in reflectivity from excitonic states as a spatially resolved probe of charge-carrier spin polarization. At electron densities ne ~ 1012 cm−2, a diffraction-limited, circularly polarized optical pump breaks symmetry between oppositely polarized magnetic states and stabilizes long-range magnetic order, with carrier polarization exceeding 80% over an 8 μm by 5 μm extent. In time-resolved measurements with pulsed optical excitation, we observe that magnetic interactions amplify the initial pump-induced spin polarization by more than an order of magnitude. The optical control of magnetism with local optical pumps will unlock advancements in spin and optical technologies and provides a versatile tool in the study of correlated phases in two-dimensional electron gases

Robotic four-dimensional pixel assembly of van der Waals solids

Van der Waals (vdW) solids can be engineered with atomically precise vertical composition through the assembly of layered two-dimensional materials(1,2). However, the artisanal assembly of structures from micromechanically exfoliated flakes(3,4) is not compatible with scalable and rapid manufacturing. Further engineering of vdW solids requires precisely designed and controlled composition over all three spatial dimensions and interlayer rotation. Here, we report a robotic four-dimensional pixel assembly method for manufacturing vdW solids with unprecedented speed, deliberate design, large area and angle control. We used the robotic assembly of prepatterned 'pixels' made from atomically thin two-dimensional components. Wafer-scale two-dimensional material films were grown, patterned through a clean, contact-free process and assembled using engineered adhesive stamps actuated by a high-vacuum robot. We fabricated vdW solids with up to 80 individual layers, consisting of 100 x 100 mu m(2) areas with predesigned patterned shapes, laterally/vertically programmed composition and controlled interlayer angle. This enabled efficient optical spectroscopic assays of the vdW solids, revealing new excitonic and absorbance layer dependencies in MoS2. Furthermore, we fabricated twisted N-layer assemblies, where we observed atomic reconstruction of twisted four-layer WS2 at high interlayer twist angles of >= 4 degrees. Our method enables the rapid manufacturing of atomically resolved quantum materials, which could help realize the full potential of vdW heterostructures as a platform for novel physics(2,5,6) and advanced electronic technologies(7,8).N