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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.10
- 수록면
- 15 - 33 (19page)
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IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8<SUP>+</SUP> T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8<SUP>+</SUP> T cells and features of IL-1R<SUP>+</SUP>CD8<SUP>+</SUP> T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8<SUP>+</SUP> T cells. Further, IL-1β enhances the effector function of CD8<SUP>+</SUP> T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8<SUP>+</SUP> T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8<SUP>+</SUP> T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8<SUP>+</SUP> T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.
목차
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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UCI(KEPA) : I410-ECN-0101-2022-517-000121202