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Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin

ABSTRACT: Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin

PROVIDER: PRJNA693812 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13496908.fastq.gz	Fastqsanger.gz
	SRR13496909.fastq.gz	Fastqsanger.gz
	SRR13496910.fastq.gz	Fastqsanger.gz
	SRR13496911.fastq.gz	Fastqsanger.gz
	SRR13496912.fastq.gz	Fastqsanger.gz

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Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin

Project description:HBV vaccine is composed of surface antigen (HBsAg) that spontaneously assembles into subvirus particles. Factors that impede its humoral immunity in 5-10% of vaccinees remain elusive. Herein we showed that the low-level interleukin-1 receptor antagonist (IL-1Ra) can predict antibody protection both in mice and humans. Mechanistically, murine IL-1Ra inhibited Tfh cell expansion and subsequent GC dependent humoral immunity, resulting in significantly weakened protection against HBV challenge. Compared to soluble antigens, HBsAg particle antigen displayed a unique capture/uptake and innate immune activation, including IL-1Ra expression, preferably of medullary sinus macrophages (MSM). In humans, a unique polymorphism in RelA/p65 binding site of IL-1Ra enhancer associated IL-1Ra levels with ethnicity dependent vaccination outcome. Therefore, the differential IL-1Ra response to particle antigens probably creates a suppressive milieu for Tfh/GC development, and neutralization of IL-1Ra would resurrect antibody response in HBV vaccine non-responders.

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Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin.

Project description:Hepatitis B virus (HBV) vaccines are composed of surface antigen HBsAg that spontaneously assembles into subviral particles. Factors that impede its humoral immunity in 5% to 10% of vaccinees remain elusive. Here, we showed that the low-level interleukin-1 receptor antagonist (IL-1Ra) can predict antibody protection both in mice and humans. Mechanistically, murine IL-1Ra-inhibited T follicular helper (Tfh) cell expansion and subsequent germinal center (GC)-dependent humoral immunity, resulting in significantly weakened protection against the HBV challenge. Compared to soluble antigens, HBsAg particle antigen displayed a unique capture/uptake and innate immune activation, including IL-1Ra expression, preferably of medullary sinus macrophages. In humans, a unique polymorphism in the RelA/p65 binding site of IL-1Ra enhancer associated IL-1Ra levels with ethnicity-dependent vaccination outcome. Therefore, the differential IL-1Ra response to particle antigens probably creates a suppressive milieu for Tfh/GC development, and neutralization of IL-1Ra would resurrect antibody response in HBV vaccine nonresponders.

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