Biology subjects

Awali, S.

Publications and source records attributed to Awali, S..

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↗

bioRxiv2024

Differential composition of lymphocyte subpopulations and activation between the hypertensive Bph/2 and normotensive Bpn/3 mouse strains

Numerous studies point to a role for the immune system in various animal models of hypertension. However, little is known about the immune system of Bph/2 mice, a spontaneously hypertensive strain. To address this, we conducted a comprehensive comparison of immune cell composition and response to polyclonal T cell activation in hypertensive Bph/2 mice and normotensive Bpn/3 control mice. We quantified immune cell populations by flow cytometry from spleen and inguinal, brachial and mesenteric lymph nodes. While composition of myeloid immune cell types was largely comparable between strains, we observed differences in B and T cell subpopulations. Specifically, we found an increased percentage of IgM+ IgDLo and IgM+ IgD-B cells in Bph/2 mice, suggesting greater baseline B cell activation. In addition, we observed a decreased percentage of CD4 effector memory T cells and CD8 central memory T cells. The diminished proportion of memory T cells in Bph/2 mice correlated with decreased proliferation and cytokine response of splenic T cells to polyclonal T cell activation. In splenic T cells from Bph/2 mice 24 h after activation we observed a pronounced decrease in the majority of T cell cytokines. At 120 h after activation, the Th1 and Th17 cytokine responses of splenic T cells from Bph/2 mice were decreased, but other T cell cytokines were largely comparable. Overall, the data suggest a decreased percentage of memory T cells in Bph/2 mice that correlates with markedly diminished proliferation and a reduced cytokine response to polyclonal activation.

immunology↗