Hepсidin regulation of adaptive immune cell functions

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Abstract

The peptide hormone hepcidin is a key regulator of iron metabolism. Primarily synthesized in the liver, it controls the absorption of iron ions by enterocytes and iron export from cells. Hepcidin acts by binding to its principal target, protein ferroportin, inducing its internalization and degradation, thereby blocking the release of iron ions from cells. Changes in the intracellular level of iron ions are critical for immune cell function. The synthesis of hepcidin, and consequently ferroportin, increases during inflammation in response to proinflammatory cytokines and to infectious agents that stimulate toll-like receptors. Lymphocyte proliferation is a key stage in the development of the adaptive immune response, and iron is essential for this process. The review analyzes current understanding of the mechanisms of hepcidin immunoregulatory activity in relation to the adaptive immunity cells. Regulation of the intracellular levels of iron ions by hepcidin affects the activation and proliferation of T- and B-lymphocytes, directs differentiation of effector subpopulations of T-helper lymphocytes and cytotoxic T-lymphocytes, the formation of memory B-cells and antibody production. The relevance of systematizing knowledge about the mechanisms of regulation of iron metabolism and the immunoregulatory activity of hepcidin is determined by the widespread prevalence of iron deficiency conditions and popularity of iron-containing drugs. Understanding the mechanisms of targeted regulation of iron metabolism has profound fundamental and practical significance and opens up new prospects for the treatment of iron deficiency, infectious, oncological and neurodegenerative diseases.

About the authors

E. G. Orlova

Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences; Ye.A. Vagner Perm State Medical University

Author for correspondence.
Email: orlova_katy@mail.ru
ORCID iD: 0000-0003-1195-8962

DSc (Biology), Leading Researcher

Russian Federation, Perm; Perm

O. L. Gorbunova

Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences

Email: orlova_katy@mail.ru
ORCID iD: 0000-0002-7580-6848

PhD (Biology), Researcher

Russian Federation, Perm

N. P. Loginova

Ye.A. Vagner Perm State Medical University

Email: natalitsa@yandex.ru
ORCID iD: 0000-0001-8597-2682

DSc (Medicine), Associate Professor, Head of the Department of Histology, Embryology and Cytology

Russian Federation, Perm

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