RT info:eu-repo/semantics/article
T1 Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation
A1 Rodriguez-Cetina Biefer, Héctor
A1 Heinbokel, Timm
A1 Uehara, Hirofumi
A1 Camacho, Virginia
A1 Minami, Koichiro
A1 Nian, Yeqi
A1 Koduru, Suresh
A1 El Fatimy, Rachid
A1 Ghiran, Ionita
A1 Trachtenberg, Alexander J.
A1 Fuente García, Miguel Ángel de la
A1 Azuma, Haruhito
A1 Akbari, Omid
A1 Tullius, Stefan G.
A1 Vasudevan, Anju
A1 Elkhal, Abdallah
K1 Mast cells
K1 Mastocitos
K1 T cells
K1 Células T
K1 Antigen presentation
K1 Presentación de antígeno
AB Background: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. Objective: The objective of this study is to further dissect the mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T-cell activation. Methods: Isolated dendritic cells and bone marrow–derived mast cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T-cell fate in vitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was investigated in vivo by using wild-type C57BL/6, MC−/−, MHC class II−/−, Wiskott-Aldrich syndrome protein (WASP)−/−, 5C.C7 recombination-activating gene 2 (Rag2)−/−, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD+ on the systemic immune response in the context of Listeria monocytogenes infection. Results: Our in vivo and in vitro findings indicate that after NAD+ administration, MCs exclusively promote CD4+ T-cell differentiation, both in the absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor signaling machinery. More importantly, although treatment with NAD+ resulted in decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to administration of lethal doses of L monocytogenes. Conclusions: Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity through MCs exclusively and underscores the therapeutic potential of NAD+ in the context of primary immunodeficiencies and antimicrobial resistance.
PB Elsevier
SN 0091-6749
YR 2018
FD 2018
LK http://uvadoc.uva.es/handle/10324/44608
UL http://uvadoc.uva.es/handle/10324/44608
LA eng
NO Journal of Allergy and Clinical Immunology, 2018, vol. 142, n. 6. p. 1894-1908
NO Producción Científica
DS UVaDOC
RD 22-dic-2024