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Virology Research Journal
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Volume 2
Page 41
allied
academies
IMMUNOLOGY AND CELL BIOLOGY
BACTERIOLOGY AND INFECTIOUS DISEASES
&
Global Summit on
Global Congress on
J u n e 2 5 - 2 6 , 2 0 1 8 | A m s t e r d a m , N e t h e r l a n d s
Joint Event on
NOVEL IMMUNE REGULATORY PROPERTIES OF NAD+ AND ITS
BENEFITS IN DISEASE SCENARIOS
Abdallah Elkhal
Harvard Medical School, USA
I
t is well known that MHC-TCR activation following pathogen invasion dictates CD4+ T cell differentiation. More recently, a second
mechanism involving TLRs and NLRs pathways have been shown to regulate CD4+ T cell differentiation as well. Both pathways
require antigen presenting cells in particular dendritic cells (DCs). Moreover, CD4+ T cell fate is tightly regulated by cytokine
milieu (produced by DCs) and major transcription factors that give rise to specific T helper subset (Th1, Th2, Th17 and regulatory
T cells (Tregs)). Alterations in DC-mediated CD4+ T cell regulation pathway leads to a myriad of diseases including atopic
disorders, autoimmune, primary immunodeficiency, infections and cancer. In our studies, we demonstrated that NAD+ regulates
CD4+ T cell differentiation independently of cytokine milieu and well established transcription factors. It is well established
that the transcription factor T-bet is critical for Th1 differentiation. Our results demonstrated that in the presence of NAD+, the
frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1
polarizing conditions. Moreover, we showed a robust and unique immunoregulatory property of NAD+ that are independent of
CD4+CD25+Foxp3+ Tregs, a unique T cell lineage that is essential for maintaining immune tolerance and homeostasis. Finally,
our findings indicate that following NAD+ administration MCs, exclusively, promote CD4+ T cell differentiation, both in absence
of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T cell differentiation independently of
MHC-II and TCR signaling machinery. Collectively, our study unravels a novel cellular and molecular pathway that regulates innate
and adaptive immunity via MCs, exclusively. This untapped novel and distinct pathway may serve as an alternative to bypass
certain inflammatory conditions and pave the way for novel therapeutic approaches in the context of autoimmune diseases,
transplantation, primary immunodeficiencies and antimicrobial resistance.
aelkhal@partners.orgVirol Res J 2018, Volume 2