Biological Sciences
http://hdl.handle.net/10211.3/163086
2024-03-28T12:31:20ZObesity impairs gd T cell homeostasis and antiviral function in humans.
http://hdl.handle.net/10211.3/164755
Obesity impairs gd T cell homeostasis and antiviral function in humans.
Costanzo, A.; Taylor, K.; Dutt, S.; Han, P.; Fujioka, K.; Jameson, J.M.
Obese patients are susceptible to increased morbidity and mortality associated with infec-tious diseases such as influenza A virus. γδ T cells and memory αβ T cells play key roles in reducing viral load by rapidly producing IFN-γ and lysing infected cells. In this article we an-alyze the impact of obesity on T lymphocyte antiviral immunity. Obese donors exhibit a re-duction in γδ T cells in the peripheral blood. The severity of obesity negatively correlates with the number of γδ T cells. The remaining γδ T cells have a skewed maturation similar to that observed in aged populations. This skewed γδ T cell population exhibits a blunted anti-viral IFN-γ response. Full γδ T cell function can be restored by potent stimulation with 1-Hy-droxy-2-methyl-buten-4yl 4-diphosphate (HDMAPP), suggesting that γδ T cells retain the ability to produce IFN-γ. Additionally, γδ T cells from obese donors have reduced levels of IL-2Rα. IL-2 is able to restore γδ T cell antiviral cytokine production, which suggests that γδ
T cells lack key T cell specific growth factor signals. These studies make the novel finding that the γδ T cell antiviral immune response to influenza is compromised by obesity. This has important implications for the development of therapeutic strategies to improve vaccination and antiviral responses in obese patients.
2015-01-01T00:00:00ZDendritic epidermal gd T cell ligands are rapidly and locally expressed by keratinocytes following cutaneous wounding
http://hdl.handle.net/10211.3/164753
Dendritic epidermal gd T cell ligands are rapidly and locally expressed by keratinocytes following cutaneous wounding
Komori, K.; Witherden, D.A.; Kelly, R.; Sendaydiego, K.; Jameson, J.M.; Teyton, L.; Havran, W.L.
TCR specific activation is pivotal to dendritic epidermal T cell (DETC) function during cutaneous
wound repair. However, DETC TCR ligands are uncharacterized and little is known about their
expression patterns and kinetics. Using soluble DETC TCR tetramers, we demonstrate that DETC
TCR ligands are not constitutively expressed in healthy tissue, but are rapidly upregulated
following wounding on keratinocytes bordering wound edges. Ligand expression is tightly
regulated with down-modulation following DETC activation. Early inhibition of TCR-ligand
interactions using DETC TCR tetramers delays wound repair in vivo, highlighting DETC as rapid
responders to injury. This first visualization of DETC TCR ligand expression provides novel
information about how ligand expression impacts early stages of DETC activation and wound
repair.
Published in final edited form as:
J Immunol. 2012 April 1; 188(7): 2972–2976. doi:10.4049/jimmunol.1100887.
2012-01-01T00:00:00ZHigh Fat Diet Causes Depletion of Intestinal Eosinophils Associated With Intestinal Permeability
http://hdl.handle.net/10211.3/164751
High Fat Diet Causes Depletion of Intestinal Eosinophils Associated With Intestinal Permeability
Johnson, J.; Costanzo, A.; Gareau, M.; Armando, A.; Quehenberger, O.; Jameson, J.M.; Olefsky, J.
The development of intestinal permeability and the penetration of microbial products are key factors associated with the onset of metabolic disease. However, the mechanisms un-derlying this remain unclear. Here we show that, unlike liver or adipose tissue, high fat diet (HFD)/obesity in mice does not cause monocyte/macrophage infiltration into the intestine or pro-inflammatory changes in gene expression. Rather HFD causes depletion of intestinal eosinophils associated with the onset of intestinal permeability. Intestinal eosinophil num-bers were restored by returning HFD fed mice to normal chow and were unchanged in lep-tin-deficient (Ob/Ob) mice, indicating that eosinophil depletion is caused specifically by a high fat diet and not obesity per se. Analysis of different aspects of intestinal permeability in HFD fed and Ob/Ob mice shows an association between eosinophil depletion and ileal paracelullar permeability, as well as leakage of albumin into the feces, but not overall per-meability to FITC dextran. These findings provide the first evidence that a high fat diet causes intestinal eosinophil depletion, rather than inflammation, which may contribute to de-fective barrier integrity and the onset of metabolic disease.
2015-01-01T00:00:00Z