ABSTRACT
Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.
Subject(s)
Colitis , Eosinophilia , Inflammatory Bowel Diseases , Nuclear Receptor Subfamily 1, Group F, Member 3 , Animals , Mice , Anti-Infective Agents/metabolism , Eosinophilia/metabolism , Immunity, Innate , Inflammation/metabolism , Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/metabolism , Lymphocytes/metabolism , Mice, Inbred C57BL , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , RetinoidsABSTRACT
Single-beam laser Doppler measurements of flow velocity are only sensitive to the velocity component parallel to the optical axis. We describe a simple modification to a standard Doppler optical coherence tomography (OCT) system using a single sample beam that provides velocity information from multiple angles within the beam. By introducing a glass plate midway into the OCT beam path, the sample beam is divided into several components, each with a different group delay and each providing a separate interferogram with its own effective Doppler angle. By combining the Doppler shift measured in each of these component interferograms, the flow velocity vector is fully determined.
Subject(s)
Tomography, Optical Coherence/instrumentation , Tomography, Optical Coherence/methods , Imaging, Three-Dimensional , Models, Statistical , Normal Distribution , Phantoms, ImagingABSTRACT
We present a fiber-based, low-coherence interferometer that significantly reduces phase noise by incorporating a second, narrowband, continuous-wave light source as a phase reference. By incorporating this interferometer into a Doppler OCT system, we demonstrate significant velocity noise reduction in reflective and scattering samples using processing techniques amenable to real-time implementation. We also demonstrate 90% suppression of velocity noise in a flow phantom.
