Neuroimmunology and Inflammation Program

Karen Bulloch
Research Associate Professor

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The Neuroimmunology and Inflammation Program, headed by Dr. Karen Bulloch, in conjunction with the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, characterizes a novel immune cell population, termed brain dendritic cells, in the normal and diseased central nervous system. Dendritic cells, initially discovered by the University's Dr. Ralph Steinman and Dr. Zanvil Cohn, are essential in orchestrating the body's immune response to pathogenic and toxic antigens. Dendritic cells also play an important role in maintaining tolerance in the body to protect against autoimmune diseases.

Brain dendritic cells were identified using a transgenic mouse model developed at the University (Linquist et al., 2004), which expresses enhanced yellow fluorescent protein under the control of the CD11c gene promoter (a marker for dendritic cells throughout the body). Dr. Bulloch and the program's scientists further characterized brain dendritic cells in neonatal, young, adult and aging brains, as well as, their presence following seizures and stroke. It was further shown that brain dendritic cells are competent inducers of the T cell immune response.

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Currently, the program's scientists are working on evaluating the function of brain dendritic cells following viral infection and in mouse models of inflammation and neurodegenerative diseases. Additional work is being carried out on understanding the role of these cells in development and in neuroendocrine-immune interactions, with our colleague Dr. Peter Harry Jellinck.

Some of the program's early data indicates that these cells respond to points of injury and infection in the brain. It is our goal to elucidate the mechanisms of response and develop new targets for therapies for a wide range of CNS damage.

Relevant Publications

  • D'Agostino PM, Gottfried-Blackmore A, Anandasabapathy N, Bulloch K. Brain dendritic cells: biology and pathology. PMID 22825593 ACTA NEUROPATHOL 2012 NOV;124(5):599-614
  • D'Agostino PM, Kwak C, Vecchiarelli HA, Toth JG, Miller JM, Masheeb ZM, McEwen BS, Bulloch K. Viral-induced encephalitis initiates distinct and functional CD103+ CD11b+ brain dendritic cell populations within the olfactory bulb. PMID 22474352 PMCID 3340999 PROC NATL ACAD SCI USA 2012 APR17;109(16):6175-80
  • Kaunzner UK, Miller MM, Gottfried-Blackmore A, Gal-Toth J, Felger JC, McEwen BS, Bulloch K. Accumulation of resident and peripheral dendritic cells in the aging CNS. PMID 20692074 PMCID NEUROBIOLOGY OF AGING epub 2010 AUG
  • Gottfried-Blackmore A, Sierra A, McEwen BS, Ge RS, Bulloch K. Microglia Express Functional 11 beta-Hydroxysteroid Dehydrogenase Type 1. PMID 20544861 GLIA 2010 AUG 1;58(10):1257-1266
  • Felger JC, Abe T, Kaunzner UW, Gottfried-Blackmore A, Gal-Toth J, McEwen BS, Iadecola C, Bulloch K. Brain dendritic cells in ischemic stroke: Time course, activation state, and origin. PMID 19914372 PMCID 2885548 BRAIN BEHAV IMMUN 2010 JUL;24(5):724-737
  • Gottfried-Blackmore A, Kaunzner UW, Idoyaga J, Felger JC, McEwen BS, Bulloch K. Acute in vivo exposure to interferon-gamma enables resident brain dendritic cells to become effective antigen presenting cells. PMID 19906988 PMCID 2791588 PROC NATL ACAD SCI USA 2009 DEC 8;106(49):20918-20923
  • Gottfried-Blackmore A , Sierra A , Jellinck PH , McEwen BS , Bulloch K. Brain microglia express steroid-converting enzymes in the mouse. J STEROID BIOCHEM MOL BIOL 2008 MAR;109(1-2):96-107
  • Sierra A , Gottfried-Blackmore A , Milner TA , Mcewen BS , Bulloch K. Steroid hormone receptor expression and function in microglia. GLIA 2008 APR 15;56(6):659-674
  • Bulloch K , Miller MM , Gal-Toth J , Milner TA , Gottfried-Blackmore A , Waters EM , Kaunzner UW , Liu K , Lindquist R , Nussenzweig MC , Steinman RM , McEwen BS. CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain. PMID 18386786 J COMP NEUROL 2008 JUN 10;508(5):687-710
  • Sierra A , Gottfried-Blackmore AC , McEwen BS , Bulloch K. Microglia derived from aging mice exhibit an altered inflammatory profile. GLIA 2007 MAR;55(4):412-424
  • Wolf OT, Dyakin V, Patel A, Vadasz C, de Leon MJ, McEwen BS, Bulloch K Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus following kainic acid (KA) treatment. BRAIN RES 2002 MAY 3;934(2):87-96
  • Bulloch K, Milner TA, Prasad A, Hsu M, Buzsaki G, McEwen BS Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal neurons following ischemia: A putative regional modulator of the CNS injury/immune response. EXP NEUROL 1998 APR;150(2):195-205
  • Bulloch K, McEwen BS, Nordberg J, Diwa A, Baird S Selective regulation of T-cell development and function by calcitonin gene-related peptide in thymus and spleen - An example of differential regional regulation of immunity by the neuroendocrine system. NEUROIMMUNOMODULATION 1998;551-562

Current Grant Support:

Peter Deane Trust
Woodin Dendritics LLC