Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling

Author:

Cao Ai-Ping12,Wang Yun-Ying2,Shen Yan-Yan2,Liu Yan-Hong2,Liu Jia-Yu2,Wang Yao2,Guo Yue2,Wang Rui-Bo2,Xie Bo-Yang2,Pan Xin2ORCID,Li Ai-Ling12,Xia Qing2,Zhang Wei-Na2,Zhou Tao12ORCID

Affiliation:

1. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310016, China

2. Nanhu Laboratory, National Center of Biomedical Analysis, Beijing 100039, China

Abstract

Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.

Funder

National Natural Science Foundation of China

Nanhu Laboratory

Publisher

MDPI AG

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