Cohen, S, Danzaki, K, and MacIver, NJ. "Nutritional effects on T-cell immunometabolism." European journal of immunology 47, no. 2 (February 2017): 225-235. (Review)
Nancie Jo MacIver, MD, PhD
My laboratory is broadly interested in how large changes in nutritional status (e.g. malnutrition or obesity) influence T cell immunity. Malnutrition can lead to immunodeficiency and increased risk of infection, whereas obesity is associated with inflammation that promotes multiple diseases including autoimmunity, type 2 diabetes, and cardiovascular disease. We have identified the adipocyte-secreted hormone leptin as a critical link between nutrition and immunity. Leptin is secreted from adipocytes in proportion to adipocyte mass and is therefore decreased in malnutrition and increased in obesity. We have found that leptin is a critical regulator of effector T cell glucose metabolism and thereby drives effector T cell activation. From these initial findings, we have established further lines of investigation, as summarized here.
(1) Determining molecular mechanisms of T cell dysfunction in malnutrition – Our goal is to identify metabolic and epigenetic mechanisms by which malnutrition and decreased leptin alter T cell function leading to increased susceptibility to infection and protection against autoimmune diseases. We study this using a mouse model of autoimmunity, experimental autoimmune encephalomyelitis (EAE).
(2) Elucidating mechanisms of T cell inflammation in obesity-induced type 2 diabetes – Our goal is to identify molecular and metabolic mechanisms by which obesity alters the Teff/Treg balance, resulting in inflammation and subsequent insulin resistance leading to type 2 diabetes. With our collaborators from UNC Chapel Hill, we are also identifying immunometabolic changes in obese animals and humans that correlate with increased susceptibility to influenza.
(3) Determining the role of insulin and IGF-1 in regulating T cell function and metabolism – Our goal is to identify how insulin influences both T cell glucose uptake and T cell differentiation/cytokine production and determine the role of insulin signaling in T cells in the setting of obesity-associated diabetes. We hypothesize that insulin has a direct role in T cell function through its abiltiy to alter T cell glucose metabolism, influence T cell cytokine production, and impact the pathophysiology of obesity-associated type 2 diabetes.
Education and Training
- Pediatric Endocrinology Fellowship, Pediatrics, Duke University, 2006 - 2009
- Pediatrics Internship & Residency, Pediatrics, Duke University, 2003 - 2006
- Ph.D., Mayo School of Health Sciences, 2003
- M.D., Mayo School of Health Sciences, 2003
Selected Grants and Awards
- Mechanisms of T cell inflammation in obesity-induced type 2 diabetes
- Identifying molecular mechanisms by which leptin and nutrition target T cell immunity in multiple sclerosis
- Regulation of T cell differentiation and metabolism in malnutrition
- Leptin as a Regulator of T Cell Metabolism and Function
Gerriets, VA, Danzaki, K, Kishton, RJ, Eisner, W, Nichols, AG, Saucillo, DC, Shinohara, ML, and MacIver, NJ. "Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity." European journal of immunology 46, no. 8 (August 2016): 1970-1983.
Saucillo, DC, Gerriets, VA, Sheng, J, Rathmell, JC, and Maciver, NJ. "Leptin metabolically licenses T cells for activation to link nutrition and immunity." J Immunol 192, no. 1 (January 1, 2014): 136-144.
Gerriets, VA, and MacIver, NJ. "Role of T cells in malnutrition and obesity." Frontiers in immunology 5 (January 2014): 379-. (Review)
MacIver, NJ, Michalek, RD, and Rathmell, JC. "Metabolic regulation of T lymphocytes." Annu Rev Immunol 31 (2013): 259-283. (Review)
MacIver, NJ, Blagih, J, Saucillo, DC, Tonelli, L, Griss, T, Rathmell, JC, and Jones, RG. "The liver kinase B1 is a central regulator of T cell development, activation, and metabolism." J Immunol 187, no. 8 (October 15, 2011): 4187-4198.
Maciver, NJ, Jacobs, SR, Wieman, HL, Wofford, JA, Coloff, JL, and Rathmell, JC. "Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival." J Leukoc Biol 84, no. 4 (October 2008): 949-957. (Review)