About

Nancie MacIver is an Associate Professor of Nutrition in the Department of Nutrition and also serves as a Division Chief of Pediatric Endocrinology at UNC. She is a physician scientist with a research interest in nutritional immunology and immunometabolism. Her laboratory is broadly interested in how large changes in nutritional status, such as undernutrition or obesity, and nutritionally regulated hormones, alter T cell immunity.

Research topics

• Biology
• Immunology
• Medicine
• Internal medicine
• Computer Science
• Endocrinology
• Environmental health
• Biochemistry
• Computational biology
• Genetics
• Programming language

Selected publications

• Irgm1 Restrains CD8 ⁺ T Cell Cytokine Production and Apoptosis via Cell‐Extrinsic Regulation of Type I Interferon Signaling

  European Journal of Immunology · 2026-03-29

  articleOpen accessSenior author

  ABSTRACT Immunity‐related GTPases (IRGs) are a family of proteins that maintain cellular homeostasis by promoting autophagy and mitophagy. Mutations in human IRGM and genetic deletion of mouse Irgm1 have been linked to increased severity of inflammatory bowel disease, cancer, sepsis, and various infections. While IRGM/Irgm1 are known cell‐intrinsic regulators of inflammation, their roles in T cell function remain poorly understood. We previously demonstrated that Irgm1 deficiency leads to increased production of proinflammatory mediators, including Granzyme B and interferon‐γ, and increased apoptosis in CD8 + T cells. Here, we show that Irgm1 deficiency also alters Granzyme B production and impairs virus‐specific CD8 + T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Using T cell‐specific Irgm1 knockout mice and adoptive transfer experiments, we unexpectedly found that Irgm1 regulates CD8 + T cell responses through a cell‐extrinsic mechanism. Transcriptomic and genetic analyses identified type I interferons (IFNs) as key mediators of this effect. These findings reveal a previously unrecognized, cell‐extrinsic role for Irgm1 in regulating CD8 + T cell survival and function by modulating the inflammatory environment. Our results suggest that IRGM/Irgm1 acts as a critical immune rheostat, restraining pathological inflammation and modulating T cell responses in infection and autoimmunity.

  PublisherOA PDFDOI

• Author response for "Irgm1 restrains CD8+ T cell cytokine production and apoptosis via cell-extrinsic regulation of Type I interferon signaling"

  2025-11-24

  peer-reviewSenior author
  PublisherDOI

• Author response for "Irgm1 restrains CD8+ T cell cytokine production and apoptosis via cell-extrinsic regulation of Type I interferon signaling"

  2025-09-04

  peer-reviewSenior author
  PublisherDOI

• Author response for "Irgm1 restrains CD8+ T cell cytokine production and apoptosis via cell-extrinsic regulation of Type I interferon signaling"

  2025-10-28

  peer-reviewSenior author
  PublisherDOI

• Targeting IL-6 receptor mediated metabolic pathways to control Th17 cell differentiation and inflammatory responses

  Frontiers in Immunology · 2025-08-27 · 4 citations

  articleOpen accessSenior authorCorresponding

  Interleukin-6 (IL-6) is a multifunctional cytokine that plays important roles in inflammation. Several studies have shown that IL-6 regulates various aspects of T cell function, including the differentiation of CD4 + T cells into the pro-inflammatory Th17 subset. Given the tight link between T cell metabolism and function, and the role of IL-6 in regulating cellular metabolism across tissues, we investigated the role of IL-6 signaling in Th17 cell metabolism. Using T cell specific IL-6 receptor (IL-6R) conditional knockout mice and littermate controls, we found that IL-6R signaling regulates the proportions of CD4 + and CD8 + T cells and drives CD4 + T cell differentiation into Th17 cells. We also found that IL-6R signaling is required for Th17 cell glycolytic metabolism. In T cell-specific IL-6R knockout mice, Th17 cells had reduced glucose uptake and glycolysis, as well as decreased expression of key glycolytic enzymes, while showing increased basal oxygen consumption. However, we also found that IL-6R signaling enhanced oxidative capacity and mitochondrial coupling efficiency in Th17 T cells. Importantly, inhibition of lactate dehydrogenase using FX11 selectively impaired Th17 cell differentiation with minimal effects on Treg cells. These findings suggest that targeting metabolic pathways regulated by IL-6R signaling can selectively inhibit inflammatory Th17 responses, offering a potential strategy for controlling IL-6 mediated inflammation.

  PublisherOA PDFDOI

• Insulin and IGF-1 have both overlapping and distinct effects on CD4+ T cell mitochondria, metabolism, and function

  UNC Libraries · 2024-10-18

  articleOpen access
  PublisherDOI

• Metformin as a Therapeutic Agent for Obesity-Associated Immune Dysfunction

  Journal of Nutrition · 2024-07-05 · 6 citations

  reviewSenior authorCorresponding
  PublisherDOI

• Metformin use associated with lower rate of hospitalization for influenza in individuals with diabetes

  Diabetes Obesity and Metabolism · 2024-05-14 · 1 citations

  articleSenior authorCorresponding

  AIM: To investigate if patients with diabetes taking metformin have better outcomes versus those not taking metformin following an emergency room visit for influenza. METHODS: Using electronic medical records, we performed a retrospective chart review of all adult patients with a diagnosis of diabetes seen in any Duke University Medical Center-affiliated emergency department for influenza over a 6-year period. We documented patient characteristics and comorbidities, and compared outcomes for patients taking metformin versus patients not taking metformin using both univariable and multivariable analyses. Our primary outcome was hospital admission rate. Secondary outcomes were in-hospital length of stay and in-hospital death. RESULTS: Our cohort included 1023 adult patients with diabetes, of whom 59.9% were female. The mean age was 62.9 years, 58.4% were African American, 36.1% were White, and 81.9% were obese or overweight. Of these patients, 347 (34%) were taking metformin. Patients with diabetes taking metformin were less likely to be hospitalized following an emergency department visit for influenza than patients with diabetes not taking metformin (56.8% vs. 70.1%; p < 0.001). Of those patients admitted, there was no statistically significant difference in length of stay or death. CONCLUSIONS: In patients with diabetes, metformin use is associated with lower rate of hospitalization following an emergency department visit for influenza.

  PublisherDOI

• Inflammation and Metabolism of Influenza-Stimulated Peripheral Blood Mononuclear Cells From Adults With Obesity Following Bariatric Surgery

  UNC Libraries · 2024-08-14

  articleOpen access

  BACKGROUND: Obesity dysregulates immunity to influenza infection. Therefore, there is a critical need to investigate how obesity impairs immunity and to establish therapeutic approaches that mitigate the impact of increased adiposity. One mechanism by which obesity may alter immune responses is through changes in cellular metabolism. METHODS: We studied inflammation and cellular metabolism of peripheral blood mononuclear cells (PBMCs) isolated from individuals with obesity relative to lean controls. We also investigated if impairments to PBMC metabolism were reversible upon short-term weight loss following bariatric surgery. RESULTS: Obesity was associated with systemic inflammation and poor inflammation resolution. Unstimulated PBMCs from participants with obesity had lower oxidative metabolism and adenosine triphosphate (ATP) production compared to PBMCs from lean controls. PBMC secretome analyses showed that ex vivo stimulation with A/Cal/7/2009 H1N1 influenza led to a notable increase in IL-6 with obesity. Short-term weight loss via bariatric surgery improved biomarkers of systemic metabolism but did not improve markers of inflammation resolution, PBMC metabolism, or the PBMC secretome. CONCLUSIONS: These results show that obesity drives a signature of impaired PBMC metabolism, which may be due to persistent inflammation. PBMC metabolism was not reversed after short-term weight loss despite improvements in measures of systemic metabolism.

  PublisherDOI

• Author response for "Metformin use associated with lower rate of hospitalization for influenza in individuals with diabetes"

  2024-04-25

  peer-reviewSenior author
  PublisherDOI

Recent grants

• NIH Grant K08DK087944

  NIH · $678k · 2015

• Mechanisms of T cell inflammation in obesity-induced type 2 diabetes

  NIH · $1.8M · 2015–2020

Frequent coauthors

• Jeffrey C. Rathmell

  Vanderbilt University Medical Center

  51 shared

• Amanda Nichols

  34 shared

• Gregory A. Taylor

  Duke University

  21 shared

• Sarah R. Jacobs

  Albert Einstein College of Medicine

  20 shared

• Valerie A. Gerriets

  California Northstate University

  19 shared

• Mari L. Shinohara

  18 shared

• Yazan Alwarawrah

  University of North Carolina at Chapel Hill

  16 shared

• Andrew N. Macintyre

  Duke University

  13 shared

Education

• MD-PhD, Medicine/Immunology

  Mayo Clinic Minnesota

  2003

• BA, Mathematics

  Johns Hopkins University

  1995