Publications by authors named "Abhinav Arneja"

4 Publications

  • Page 1 of 1

Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia.

Nat Commun 2021 03 12;12(1):1645. Epub 2021 Mar 12.

Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA.

Anemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.
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http://dx.doi.org/10.1038/s41467-021-21938-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955080PMC
March 2021

Qualitatively different T cell phenotypic responses to IL-2 versus IL-15 are unified by identical dependences on receptor signal strength and duration.

J Immunol 2014 Jan 2;192(1):123-35. Epub 2013 Dec 2.

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;

IL-2 and IL-15 are common γ-chain family cytokines involved in regulation of T cell differentiation and homeostasis. Despite signaling through the same receptors, IL-2 and IL-15 have non-redundant roles in T cell biology, both physiologically and at the cellular level. The mechanisms by which IL-2 and IL-15 trigger distinct phenotypes in T cells remain elusive. To elucidate these mechanisms, we performed a quantitative comparison of the phosphotyrosine signaling network and resulting phenotypes triggered by IL-2 and IL-15. This study revealed that the signaling networks activated by IL-2 or IL-15 are highly similar and that T cell proliferation and metabolism are controlled in a quantitatively distinct manner through IL-2/15R signal strength independent of the cytokine identity. Distinct phenotypes associated with IL-2 or IL-15 stimulation therefore arise through differential regulation of IL-2/15R signal strength and duration because of differences in cytokine-receptor binding affinity, receptor expression levels, physiological cytokine levels, and cytokine-receptor intracellular trafficking kinetics. These results provide important insights into the function of other shared cytokine and growth factor receptors, quantitative regulation of cell proliferation and metabolism through signal transduction, and improved design of cytokine based clinical immunomodulatory therapies for cancer and infectious diseases.
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http://dx.doi.org/10.4049/jimmunol.1302291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950894PMC
January 2014

Cell patterning on biological gels via cell spraying through a mask.

Tissue Eng 2005 May-Jun;11(5-6):701-8

Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.

We present an easily applicable and inexpensive method for patterning cells on arbitrary surfaces including biological gels with little loss of viability or function. Single-cell suspensions of human umbilical vein endothelial cells and NIH 3T3 fibroblasts were sprayed with an off-the-shelf airbrush through a mask to create 100-microm scale patterns on collagen gels. Three-dimensional patterns were created by layering a collagen gel on top of the first pattern and patterning the top gel. Coculture of rat hepatocytes with NIH 3T3 patterns on collagen gels resulted in localized increased activity of cytochrome P-450 along the pattern. These results suggest that cell spraying is a useful tool for the study of heterotypic cellular interactions and tissue-engineering applications on biologically relevant matrices, and for the creation of three-dimensional cell patterns in vitro.
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http://dx.doi.org/10.1089/ten.2005.11.701DOI Listing
May 2006