MSTPublications: July 2018
Congratulations to all of our MSTP students on their successful publications! Take a look at the great work our students are doing.
CD4+ Regulatory T Cells Exert Differential Functions during Early and Late Stages of the Immune Response to Respiratory Viruses.
Rogers MC, Lamens KD, Shafagati N, Johnson M, Oury TD, Joyce S, Williams JV.
J Immunol. 2018 Jul 11. pii: ji1800096. doi: 10.4049/jimmunol.1800096. [Epub ahead of print]
Acute respiratory virus infections are associated with "T cell impairment," in which virus-specific T cells in the lung fail to produce proinflammatory cytokines or other cytotoxic molecules that aid in clearing the infection. It is thought that T cell impairment protects the lung from immune-mediated damage, since this tissue heals poorly after injury (we also know that at least some lung injury from infection is due to immunopathology rather than to damage caused by the virus itself). CD4+ regulatory T cells (Tregs) suppress effector T cell responses and have a role in dampening T cell responses in the lung during acute infection. The Williams lab studies human metapneumovirus (HMPV), a leading cause of lower respiratory tract infection in both pediatric and elderly populations. In this project we found that Tregs impair CD8+ T cell function and limit immunopathology during HMPV infection, but as a consequence they allow the virus to replicate to higher titers. Interestingly, we discovered that Tregs have an essential role in priming the immune response to infection. Migration of dendritic cells from the lung to the draining lymph node was impaired in the absence of Tregs, while virus-specific CD8+ T cells failed to efficiently migrate from the lymph node to the lung to initiate the adaptive immune response. However, by simply delaying Treg depletion until after immune priming, we saw improved CD8+ T cell responses and faster virus clearance. These data highlight the duality of Tregs in both promoting and restraining immune responses in respiratory virus infection. This work builds on that done by John Erickson, a Vandy MSTP alumnus, who originally discovered that inhibitory receptors contribute to T cell impairment. The Williams Lab continues to grow and thrive in its new home in Pittsburgh! (By Meredith Rogers, M3)
Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults.
Moore EE, Liu D, Pechman KR, Terry JG, Nair S, Cambronero FE, Bell SP, Gifford KA, Anderson AW, Hohman TJ, Carr JJ, Jefferson AL.
J Am Heart Assoc. 2018 Jun 26;7(13). pii: e009041. doi: 10.1161/JAHA.118.009041.
The connection between heart health and brain health is well established, though precise pathways must be identified to allow for the application of effective interventions. Using data from the Vanderbilt Memory & Aging Project, we found that increased LV mass index, an early marker preceding overt left ventricular hypertrophy, relates to white matter damage on neuroimaging, particularly among those with cognitive impairment. Subtle left ventricular remodeling may lead to subclinical ischemia, causing white matter damage. (By Elizabeth Moore, G1)
Neurofilament relates to white matter microstructure in older adults.
Moore EE, Hohman TJ, Badami FS, Pechman KR, Osborn KE, Acosta LMY, Bell SP, Babicz MA, Gifford KA, Anderson AW, Goldstein LE, Blennow K, Zetterberg H, Jefferson AL.
Neurobiol Aging. 2018 Jun 28;70:233-241. doi: 10.1016/j.neurobiolaging.2018.06.023. [Epub ahead of print]
Understanding the pathologic correlates of novel cerebrospinal fluid biomarkers for neurodegenerative diseases is critical to optimize their clinical utility in both diagnosis and prognosis. Based on data from the Vanderbilt Memory & Aging Project, we found that increased CSF levels of neurofilament light, a biomarker of axonal damage, correlated with white matter damage on neuroimaging. The associations were strongest among those with cognitive impairment and those without CSF evidence of amyloid-beta accumulation, suggesting that increased CSF NFL may indicate white matter damage as a possible etiology of cognitive decline among those without amyloid pathology. (By Elizabeth Moore, G1)
Psychometric Evaluation of the Short Sensory Profile in Youth with Autism Spectrum Disorder.
Williams ZJ, Failla MD, Gotham KO, Woynaroski TG, Cascio C.
J Autism Dev Disord. 2018 Jul 17. doi: 10.1007/s10803-018-3678-7. [Epub ahead of print]
As of the last edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the diagnostic criteria for Autism Spectrum Disorder (ASD) were changed to include a "Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment." The Short Sensory Profile (SSP), a parent questionnaire, is commonly used to assess these sensory features in children with ASD in clinical and research settings. However, the SSP was developed in children with typical development, and its properties were not validated in a group of children with ASD, In this article, we found that the SSP likely measures different traits in children with and without ASD, causing some of the scores on the questionnaire to be misleading when reported for those children. We discuss reasons for this discrepancy and recommend that researchers switch to alternative measures of these constructs. (By Zack Williams, M2)
Alex Sundermann’s October 2017 paper, “Leiomyomas in pregnancy and spontaneous abortion,” was selected for the American Board of Obstetrics and Gynecology Reading List for Maintenance of Certification. Congratulations, Alex!
Higher Aortic Stiffness is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.
Jefferson AL, Cambronero FE, Liu D, Moore EE, Neal JE, Terry JG, Nair S, Pechman KR, Rane S, Davis LT, Gifford KA, Hohman TJ, Bell SP, Wang TJ, Beckman JA, Carr JJ.
Circulation. 2018 Jul 17. doi: 10.1161/CIRCULATIONAHA.118.032410. [Epub ahead of print]
Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities.
Osborn KE, Liu D, Samuels LR, Moore EE, Cambronero FE, Acosta LMY, Bell SP, Babicz MA, Gordon EA, Pechman KR, Davis LT, Gifford KA, Hohman TJ, Blennow K, Zetterberg H, Jefferson AL.
Neurobiol Aging. 2018 Aug;68:18-25. doi: 10.1016/j.neurobiolaging.2018.03.028. Epub 2018 Apr 3.
APOE genotype modifies the association between central arterial stiffening and cognition in older adults.
Cambronero FE, Liu D, Neal JE, Moore EE, Gifford KA, Terry JG, Nair S, Pechman KR, Osborn KE, Hohman TJ, Bell SP, Sweatt JD, Wang TJ, Beckman JA, Carr JJ, Jefferson AL.
Neurobiol Aging. 2018 Jul;67:120-127. doi: 10.1016/j.neurobiolaging.2018.02.009.
Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta.
Barke TL, Goldstein JA, Sundermann AC, Reddy AP, Linder JE, Correa H, Velez-Edwards DR, Aronoff DM.
Am J Reprod Immunol. 2018 Jul 9:e13020. doi: 10.1111/aji.13020. [Epub ahead of print]
Melissa Bloodworth’s recent paper, “Glucagon-like peptide-1 receptor signaling attenuates RSV-induced type 2 responses and immunopathology,” was featured in the VUMC Reporter.
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