Nav: Home

Study explores emerging role of NAD+ in innate and adaptive immune responses

February 23, 2018

Researchers at Brigham and Women's Hospital (BWH) have discovered a new cellular and molecular pathway that regulates CD4+ T cell response--a finding that may lead to new ways to treat diseases that result from alterations in these cells. Their discovery, published online in the Journal of Allergy and Clinical Immunology, shows that administering nicotinamide adenine dinucleotide (NAD+), a natural molecule found in all living cells, shuts off the capacity of dendritic cells and macrophages to dictate CD4+ T fate. Researchers found that NAD+ administration regulated CD4+ T cells via mast cells (MCs), cells that have been mainly described in the context of allergy, exclusively.

"This is a novel cellular and molecular pathway that is distinct from the two major pathways that were previously known. Since it is distinct and since it has the ability to regulate the immune system systemically, we can use it as an alternative to bypass the current pathways," said Abdallah ElKhal, PhD, BWH Department of Surgery, senior study author.

CD4+ T helper cells and dendritic cells play a central role in immunity. Alterations or aberrant dendritic cells and T cell responses can lead to many health conditions including autoimmune diseases, infections, allergy, primary immunodeficiencies and cancer.

As of today, two major pathways have been described to regulate CD4+ T cell response. The first pathway was described by Peter C. Doherty and Rolf M. Zinkernagel (1996 Nobel prize winners) showing the requirement of MHC-TCR signaling machinery. More recently, a second mechanism involving the Pathogen or Damage Associated Molecular Patterns (PAMPs or DAMPs) was unraveled by Bruce A. Beutler and Jules A. Hoffmann (2011 Nobel Prize winners). Of importance, both pathways require antigen presenting cells (APCs) in particular dendritic cells (DCs) or macrophages (Mφ). Elkhal's novel pathway is distinct from the two previous ones and may offer a path forward for novel therapeutic approaches.

For the current study, BWH researchers performed pre-clinical trials using an experimental infection model. They showed that mast cell-mediated CD4+ T cell response protects against lethal doses of infection (Listeria monocytogenes). Mice treated with NAD+ had a dramatically increased survival rate when compared to the non-treated group.

"Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity via MCs, exclusively, and underscores the therapeutic potential of NAD+ in the context of a myriad of diseases including autoimmune diseases, hemophilia, primary immunodeficiencies and antimicrobial resistance," said Elkhal.
-end-
This work was supported by the National Institutes of Health R01NS073635 and R01MH110438, R01 HL096795 and U01 HL126497, R01AG039449. Co-authors were supported by the Swiss Society of Cardiac Surgery, FIS-ISCIII (grant PI10/02 511) and Fundación Ramón Areces (CIVP16A1843).

Brigham and Women's Hospital

Related Dendritic Cells Articles:

Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Scientists use tumor-derived dendritic cells to slow tumor growth
In the human body, so-called dendritic cells are responsible for activating our immune system.
FRET-FLIM optimization shows activity of two signaling molecules in single dendritic spine
Researchers at Max Planck Florida Institute for Neuroscience and Stanford University teamed up to optimize the imaging technique FRET-FLIM to study the activity of different signaling molecules within a single dendritic spine.
How prions kill neurons: New culture system shows early toxicity to dendritic spines
Prion diseases are fatal and incurable neurodegenerative conditions of humans and animals.
Scientists turn skin cells into heart cells and brain cells using drugs
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Discovery of CTLA-4 in dendritic cells opens new possibilities to fight cancer
CTLA-4 is also produced and secreted by dendritic cells.
A novel mechanism that helps activated dendritic cells to initiate effective immunity
Phagocytosis represents a critical innate barrier against infection and serves the clearance of extracellular microbes, infected and dying cells.
A novel mechanism that helps activated dendritic cells to initiate effective immunity
Phagocytosis represents a critical innate barrier against infection and serves the clearance of extracellular microbes, infected and dying cells.
Modified CAR T cells can preferentially target cancer cells and spare normal cells
Engineering chimeric antigen receptor (CAR) T cells to lower their affinity for the protein epithelial growth factor receptor (EGFR) made the cells preferentially recognize and eliminate tumor cells that have high amounts of EGFR while sparing normal cells that have lower amounts of the protein, according to a preclinical study.

Related Dendritic Cells Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".