Research Article: Intact lymph node homing and CD8 + T-cell priming abilities of Sprouty2-deficient dendritic cells
Abstract:
Sprouty2 (Spry2) acts as a modulator of the MAPK-ERK signaling pathway by exerting both positive and negative regulation in a highly context- and cell type-specific manner. While its role in controlling the migration of non-immune cells in growth factor-dependent contexts is well established and continuously expanding, its function as a modulator of immune cell responses has only recently begun to emerge. Spry2 appears to critically and differentially influence B- and T-cell responses, consistent with its cell type-specific nature. However, its role in dendritic cells (DCs) remains unexplored. DCs serve as the cellular link between innate and adaptive immunity, and hence, DCs rely on their ability to navigate through different tissues and migrate to distinct target locations to initiate and coordinate effective immune responses. In the present study, we show that Spry2 expression is regulated during bone marrow-derived (BM)DC maturation and established a CD11c-specific Spry2 knockout mouse model to analyze the in vitro and in vivo immune functions of Spry2-deficient DCs. Unexpectedly, we found that its complete absence does not alter essential DC immune functions. Spry2-deficient DCs display intact DC differentiation in vitro and in vivo , efficient CCR7-driven migration and effective lymph node homing in vivo . Furthermore, we demonstrate that Spry2-deficient DCs retain an unaltered ability to stimulate CD8 + T-cell activation and proliferation, ultimately resulting in normal CD8 + T-cell effector differentiation during acute viral infection. Collectively, our findings shed light on the function of Spry2 in DCs, thereby extending and reinforcing current knowledge of its diverse immunomodulatory functions.
Introduction:
The Sprouty (Spry) protein was originally identified in Drosophila as an antagonist of fibroblast growth factor signaling during tracheal branching ( 1 ). Since then, four mammalian homologues, Spry1–4, have been identified based on sequence similarity ( 1 – 4 ). Extensive research has characterized Spry proteins as key regulators of the MAPK-ERK signaling pathway. They interact with an increasing number of binding partners, thereby modulating ERK activity either positively or negatively, and can also mediate…
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