Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport

ABSTRACT

Introduction: Recently, the classification of two ‘novel’ organs, the mesentere and interstitium, was saluted as a scientific breakthrough and disseminated into mainstream media. The novelty of these findings did not pertain to the characterization of some previously unexplored phenomena, rather to the appreciation that well-established tissues may play some hitherto unexplored functions critical to system homeostasis.

Areas covered: Here we provocatively comment on the potential classification of red blood cells – by far the most abundant host cell in the human body (~ 83% of the total cells) – as an organ involved in many functions beyond gas transport. In this perspective article, we describe some of these functions with a special emphasis on the role erythrocytes play with respect to systemic metabolic homeostasis. We thus focus on how these functions modulate the cross talk of red blood cells among each other and with other cell types including immune cells.

Expert commentary: The appreciation of RBCs as an organ impacting systemic metabolic homeostasis and other cell functions while engaging in complex metabolic activity beyond oxygen transport can foster the development of novel therapeutic interventions in pathologic hypoxemia, inflammation, neurodgenerative diseases, aging, and cancer.

KEYWORDS:

• Erythrocyte
• metabolomics
• proteomics
• metabolism
• immunity

Declaration of interes

Though unrelated to the contents of the manuscript, the authors disclose that A. D’Alessandro and T. Nemkov are part of Omix Technologies, Inc. A. D’Alessandro is also an advisory board member for New Health Sciences, Inc. J.C. Zimring is on the board of directors and an advisory committee for .Rubius Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

A. D’Alessandro is supported by funds from the Linda Crnic Institute for Down Syndrome, and is a recipient of the 2017 Webb-Waring Biomedical Research Award sponsored by the Boettcher Foundation. Trainee support was provided by NIH T32 HL007171 (to T. Nemkov).