Follicular helper T cells (Tfh) support B cell development and production of antibodies, essential for a protective vaccination response. Metabolism has been linked to T cell development and the metabolic hormone leptin varies up to 10-fold among healthy people. Here, the investigators asked whether leptin levels might influence T cell development and contribute to variability in vaccine responses.
Within a cohort of 76 healthy adults, they found non-responders to influenza vaccination had on average 2.5-fold lower serum leptin levels, with non-responders 10-fold more frequent in the low leptin group (fig 1ab). Tfh counts correlate with leptin levels (fig 2). Similar observations were made among older flu vaccine recipients (age >64 yr) and young Hepatitis B vaccine (HBV) recipients. Adding leptin to T cells cultured in vitro increased Tfh markers and production of IL-21 (fig 2e).
In mice, they found leptin in areas of B cell development and leptin receptors on Tfh cells. Leptin receptor deficiency reduced antibody responses (fig 3b, c) and (consequently) allowed viral growth (panel a) in mice infected with H1N1 influenza. Tfh in leptin-receptor-deficient mice produced less IL-21 (fig 5b) and supplemental IL-21 restored most antibody production (fig 5a). IL-21 production is abrogated in T cells lacking STAT3 (fig 5g), strongly supporting a mechanism involving STAT3 and IL-21.
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| Fig 7. Leptin protects from fasting-induced susceptibility to influenza. |
They could transiently reduce serum leptin levels by ‘fasting’ (starving) mice on alternate days 5 to 15 days after infection with influenza (Fig 7a, shown above). This timing chosen to avoid interfering with T cell priming (d 0-5) and focus on peak Tfh development (starting d5). Supplemental leptin protected against influenza (panel b), underscoring the significance of this pathway.
1 comment:
Does 'supplemental' leptin improve protection in mice on a normal (non-fasting) diet?
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