Motility and Mechanical Properties of Dendritic Cells Deteriorated by Extracellular Acidosis

Lu Tong,Zhu Zeng,Ping Yue,Yingying Yang,Wei Qiu,Jin Huang

doi:10.1007/s10753-020-01373-z

Abstract

Dendritic cells (DCs) are the most powerful antigen-presenting cells known to date and play an important role in initiating and amplifying both innate and adaptive immune responses. Extracellular acidosis is an important hallmark of a variety of inflammatory processes and solid tumors. However, few studies have focused on the effect of extracellular acidosis on DCs and their functions. Cellular mechanical properties reflect the relationship between cell structure and function, including cytoskeleton (especially F-actin organization), membrane negative charges, membrane fluidity, and osmotic fragility. The study investigated the effects of extracellular acidosis on the DCs functions from the perspective of cellular migration and mechanical properties. The results showed that migration ability, F-actin contents, and membrane negative charges of DCs were reduced by extracellular acidosis no matter whether LPS stimulated its maturation or not. And these functions could not return to normal after removing acidic microenvironment, which revealed that the function impairment induced by extracellular acidosis might be irreversible. In addition, the proliferation capacity of stimulated allogeneic T cells was impaired by extracellular acidosis. Our results suggest extracellular acidosis may play an immunosuppressive role in DCs-mediated immune process.

Highlights

Dendritic cells (DCs) are the most potent antigen-presenting cells that play a crucial role in initiating and amplifying both the innate and adaptive immune responses
Because immature DCs (imDCs) capture and process antigens in peripheral tissues, and considering that many inflammatory processes as well as the growth of multiple tumors lead to the development of the acidic microenvironment in peripheral tissues, we examined the impact of extracellular acidosis on the function of DCs based on the following aspects in the study: (1) effect of extracellular acidosis on imDCs and their maturation process
DCs were incubated at potential of hydrogen (pH) 7.3 after exposure to pH 6.5 for 4 h to simulate the process of DCs that migrate out of the acidic microenvironment to the lymph node

Summary

Introduction

DCs are the most potent antigen-presenting cells that play a crucial role in initiating and amplifying both the innate and adaptive immune responses. DCs undergo two stages of differentiation: immature DCs (imDCs) and mature DCs (mDCs). The imDCs reside in non-lymphoid tissues and capture and process foreign antigens. Extracellular acidosis (or acidic microenvironment) is a significant hallmark of various inflammatory processes and solid tumors. The potential of hydrogen (pH) is an important physiological indicator of homeostasis in vivo, which usually ranges from pH 7.2 to 7.4 in the physiological state. Interstitial acidification is commonly associated with the development of inflammatory reactions against pathogens in peripheral tissues, ranging from

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Conclusion