Unveiling cytokine charge disparity as a potential mechanism for immune regulation

Jennifer M Messina; Minghao Luo; Md Shanewaz Hossan; Hadil A Gadelrab; Xiguang Yang; Anna John; Joel R Wilmore; Juntao Luo

doi:10.1016/j.cytogfr.2023.12.002

Unveiling cytokine charge disparity as a potential mechanism for immune regulation

Cytokine Growth Factor Rev. 2023 Dec 26:S1359-6101(23)00091-6. doi: 10.1016/j.cytogfr.2023.12.002. Online ahead of print.

Authors

Jennifer M Messina¹, Minghao Luo², Md Shanewaz Hossan¹, Hadil A Gadelrab¹, Xiguang Yang¹, Anna John¹, Joel R Wilmore³, Juntao Luo⁴

Affiliations

¹ Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States.
² Department of Clinical Medicine, 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
³ Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States.
⁴ Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Cancer Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States; Upstate Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY 13210, United States. Electronic address: luoj@upstate.edu.

PMID: 38184374
DOI: 10.1016/j.cytogfr.2023.12.002

Abstract

Cytokines are small signaling proteins that regulate the immune responses to infection and tissue damage. Surface charges of cytokines determine their in vivo fate in immune regulation, e.g., half-life and distribution. The overall negative charges in the extracellular microenvironment and the acidosis during inflammation and infection may differentially impact cytokines with different surface charges for fine-tuned immune regulation via controlling tissue residential properties. However, the trend and role of cytokine surface charges has yet to be elucidated in the literature. Interestingly, we have observed that most pro-inflammatory cytokines have a negative charge, while most anti-inflammatory cytokines and chemokines have a positive charge. In this review, we extensively examined the surface charges of all cytokines and chemokines, summarized the pharmacokinetics and tissue adhesion of major cytokines, and analyzed the link of surface charge with cytokine biodistribution, activation, and function in immune regulation. Additionally, we identified that the general trend of charge disparity between pro- and anti-inflammatory cytokines represents a unique opportunity to develop precise immune modulation approaches, which can be applied to many inflammation-associated diseases including solid tumors, chronic wounds, infection, and sepsis.

Keywords: Charge disparity; Cytokine; Isoelectric point; Pharmacokinetics; Tissue residence.

Publication types

Review