Biology subjects

Leipprandt, J. R.

Publications and source records attributed to Leipprandt, J. R..

3 recordsLinked to original sources

bioRxiv2025

Angiotensin II Infusion Promotes Activation and Selective Cytokine Responses in Activated CD4 and CD8 T cells

Hypertension affects roughly half of adults in the U.S. and is caused by several factors, including elevated angiotensin II (Ang II). T cells have been implicated in mechanisms of this pathology, however, data regarding T cell activation, including cytokine secretion and induction of activation markers are limited. This study investigated the hypothesis that Ang II increases T cell activation, as indicated by altered cytokine secretion and expression of surface markers associated with activation. To test this, 11-week-old C57Bl/6J male mice received saline vehicle or Ang II (490 ng/kg/min) via osmotic pump for 14 days (n=10/group) followed by immune cell isolation and ex vivo activation. Splenic T cells from Ang II-infused mice had modestly increased expression of CD25 (CD4: p=0.024, CD8: p=0.007), CD69 (CD4: p=0.017, CD8: p=0.032), and CD137 (CD8: p=0.022) 24 hours post-activation, as measured by median fluorescent intensity. The increased expression of activation markers correlated with an increase in select cytokines, including interleukin (IL)-28B (IFN{lambda}3) and interferon (IFN)-{gamma}-induced protein 10 (IP-10) at 24 hours and IFN{gamma} and IP-10 at 120 hours, while decreasing IL-23 at 120 hours. The increased expression of CD25 and CD69 suggests Ang II may increase the magnitude of T cell activation. This is further supported by the elevated induction of select cytokines all of which are associated with an antiviral response. Taken together, the data suggest Ang II modestly promotes T cell activation resulting in selective induction of cytokines associated with antiviral immunity.

immunology↗

bioRxiv2025

Sex differences in cytokine induction by activated T cells from hypertensive BPH/2 and normotensive BPN/3 mice

Over the past two decades, considerable evidence has emerged to implicate a role for the immune system in the development of hypertension. Previous studies have shown immune cells contribute to the development of hypertension in multiple animal models, however the role of the immune system in spontaneously hypertensive BPH/2 mice is not clear. In the current studies, found T cells derived from male hypertensive BPH/2 mice demonstrated an attenuated activation as compared to those derived from male BPN/3 normotensive mice. However, we also observed striking sex differences in T cell cytokine production in these strains. At 24 h post activation, in comparison to male BPH/2 mice, activated T cells from male BPN/3 mice secreted more IL-2, IL-3, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22 and TNF. In contrast to male mice, less than half of these cytokines were different between strains in female mice. We also noted marked differences in early Th17 cytokine production in which IL-17A, IL-17F and IL-22 were greater in the male, but not female, BPN/3 groups. Taken together, the data suggest that polyclonally activated T cells from male, and to a much lesser extent, female BPH/2 mice have a weaker cytokine response as compared to T cells from BPN/3 mice which may be due to an overall attenuated activation of T cells from male BPH/2 mice. Overall, while there are striking differences in T cell response between the BPH2 and BPN/3 strains in male mice, the data indicate far fewer differences between the strains in female mice.

immunology↗

bioRxiv2019

Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone

Neurodevelopmental disorder with involuntary movements (NEDIM, OMIM: 617493) is a severe, early onset neurological condition characterized by a delay in psychomotor development, hypotonia, and hyperkinetic involuntary movements. Heterozygous de novo mutations in the GNAO1 gene cause NEDIM. Go, the gene product of GNAO1, is the alpha subunit of Go, a member of the heterotrimeric Gi/o family of G-proteins. Go is found abundantly throughout the brain but the pathophysiological mechanisms linking Go functions to clinical manifestations of GNAO1-related disorders are still poorly understood. One of the most common mutant alleles among the GNAO1 encephalopathies is the c.626G>A or p.Arg209His (R209H) mutation. We developed heterozygous knock-in Gnao1+/R209H mutant mice using CRISPR/Cas9 methodology to assess whether a mouse model could replicate aspects of the NEDIM clinical pattern. Mice carrying the R209H mutation exhibited increased locomotor activity and a modest gait abnormality at 8-12 weeks. In contrast to mice carrying other mutations in Gnao1, the Gnao1+/R209H mice did not show enhanced seizure susceptibility. Levels of protein expression in multiple brain regions were unchanged from WT mice but the nucleotide exchange rate of mutant R209H Go was 9 times faster than WT. The atypical neuroleptic risperidone has shown efficacy in a patient with the R209H mutation. It also alleviated the hyperlocomotion phenotype observed in our mouse model but suppressed locomotion in WT mice as well. In this study, we show that Gnao1+/R209H mice mirror elements of the patient phenotype and respond to an approved pharmacological agent.

neuroscience↗