Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation

The vitamin B5/coenzyme A axis: A target for immunomodulation?

“…To acquire their functionality, activated T cells undergo metabolic changes that involve CoAdependent pathways [1,3]. Th17 cells play an important homeostatic role in the control of barriers and, under inflammatory stress, can acquire pathogenic features that contribute to the progression of immune-mediated diseases such as colitis, multiple sclerosis (MS), or infectious diseases [7]. This metabolic adaptation relies on the differential use of carbon sources, such as glucose, fatty acids, or amino acids, to support the acquisition of cellular programs.…”

“…Fecal short chain fatty acid levels, reduced in IBD patients [85], could simultaneously enhance colonocyte energetics and exert immunomodulatory functions [86], in part through a propionate‐mediated downmodulation of IL‐17 and IL‐22 production by γδ T cells [87]. In addition, VitB5 contributes to the regulation of Th17 immunity in IBD [7]. In addition to Pan effect on host cells, infectious agents also require Pan to sustain their metabolic activity, and inhibitors of microbial PANK enzymes, called pantothenamides, are considered potential anti‐infectious drugs in parasite, bacterial, or fungal infections [88–94].…”

“…Interestingly, dietary Pan supplementation that enhances CoA levels reduced the severity of experimental colitis or EAE. Furthermore, low serum VitB5 levels were documented in ulcerative colitis and MS patients [7]. These findings position the CoA/AcCoA ratio as a potential regulator of PKM2 activity and Th17 pathogenicity.…”

“…In addition, VitB5 contributes to the regulation of Th17 immunity in IBD [7]. In addition to Pan effect on host cells, infectious agents also require Pan to sustain their metabolic activity, and inhibitors of microbial PANK enzymes, called pantothenamides, are consid-ered potential anti-infectious drugs in parasite, bacterial, or fungal infections [88][89][90][91][92][93][94].…”

“…In the context of chronic inflammatory, infectious, tumoral, or degenerative diseases, metabolic cues and needs accumulate in damaged areas and condition the repair potential of tissues as shown in skin [4], and the maintenance of immune functions under metabolic competition between various cell types [5]. For example, in mouse models of inflammatory bowel diseases (IBD), vitamin B5 (VitB5) maintains gut mucosal barrier efficacy [6] and limits Th17 immunity [7]. Its relative deficiency is a hallmark of human IBD [8].…”