Cradle of rebellion: the relationship between bone marrow microenvironment and autoimmune diseases.

Abstract

Abnormalities in bone marrow microenvironment (BMM) represent a key mechanism closely related to the occurrence and progression of autoimmune diseases (AIDs). They involve dysfunction of critical microenvironment components: reduced supportive function of mesenchymal stromal cells (MSCs) leads to decreased secretion of the anchoring factor CXCL12, disrupting the quiescent state of hematopoietic stem cells (HSCs); dysregulation of sympathetic tone disturbs the circadian rhythm of hematopoietic cell arrangement; and abnormal proliferation of adipocytes fosters a pro-inflammatory environment. Collectively, these changes are related to a functional shift in the microenvironment from homeostasis maintenance to inflammation promotion, directionally biasing HSCs towards differentiation into pro-inflammatory immune lineages and facilitating massive release into the periphery. It establishes a pathogenic vicious cycle: peripheral autoimmune inflammation feeds back to the bone marrow (BM), further remodeling the microenvironment and perpetuating the production of aggressive immune cells, including autoreactive T cells, autoantibody-producing cells, and pro-inflammatory myeloid cells. As a result, patients experience a persistent inflammatory state that resists complete resolution, and disease progression is characterized by systemic involvement, chronicity, and relapsing course. This review focuses on the cellular and molecular components, functional roles, pathological alterations, and mechanisms of the BMM in AIDs. The review aims to provide an essential foundation for further investigation into the pathogenesis of autoimmune diseases.