Study Unravels Novel Pathway That Regulates Innate and Adaptive Immunity Via Mast Cells, Exclusively, and Underscores Therapeutic Potential of NAD+ in Myriad Diseases

Researchers at Brigham and Women's Hospital (BWH) in Boston 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. The discovery, published online on February 19, 2018 in the Journal of Allergy and Clinical Immunology, shows that administering oxidized 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. Because it is distinct and because 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. The open-access article is titled “Mast Cells Regulate CD4+ T Cell Differentiation in Absence of Antigen Presentation.” 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.
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