# Tanshinone I Enhances the Pulmonary Immune Response of CD8+ T Cells by Promoting Memory Differentiation

## TL;DR

Tanshinone I boosts lung immunity by enhancing memory CD8+ T cells, offering a new approach for vaccines against respiratory infections.

## Contribution

Tanshinone I is shown to promote pulmonary memory CD8+ T cell differentiation via nonmucosal vaccination.

## Key findings

- TSN1 induces pulmonary-resident memory CD8+ T cells through enhanced recruitment and retention.
- TSN1 increases CD44 and CD69 expression in CD8+ T cells, favoring effector memory over central memory.
- CD8+ Trm cells with CD69 expression show stronger cytolytic activity in TSN1-treated mice.

## Abstract

Objectives: Vaccination by a nonmucosal route to elicit CD8+ T cell-mediated mucosal immunity against respiratory infections presents a great challenge for the development of an effective vaccine or immunization strategy. This study aimed to explore a new strategy to address the challenge. Methods: To test this strategy, s.c. vaccinated mice were administered i.p. with tanshinone I (TSN1), a main bioactive compound found in the root of Salvia miltiorrhiza, and CD8+ T cell responses were analyzed using flow cytometry. The differentiating effects of TSN1 on CD8+ T cells from naïve mice were also evaluated in an in vitro setting. Results: Nonmucosal vaccination and administration of TSN1 induce pulmonary-resident vaccine-specific memory CD8+ T cells through increased lung-specific recruitment and retention. The improved memory response appears to result from the impact of TSN1 introduced during the primary immunization phase. Given a specific range of varying concentrations of this natural compound, it exhibits a differential effect on the memory differentiation of CD8+ T cells in the process of being activated. Effector memory T cells expand robustly relative to central memory T cells, and both memory subsets have additionally increased expression of CD44 and CD69. With more potent cytolytic activity, CD8+ Trm expressing CD69 particularly predominate the population lacking the CD69 expression in the lungs of TSN1-treated mice. Conclusions: Our study suggests that TSN1 as an important natural compound may hold great promise for novel approaches to the design and development of a more practical and efficient vaccination strategy to generate effective respiratory mucosal immunity.