Bone marrow and the control of immunity

Abstract

Bone marrow is thought to be a primary hematopoietic organ. However, accumulated evidences demonstrate that active function and trafficking of immune cells, including regulatory T cells, conventional T cells, B cells, dendritic cells, natural killer T (NKT) cells, neutrophils, myeloid-derived suppressor cells and mesenchymal stem cells, are observed in the bone marrow. Furthermore, bone marrow is a predetermined metastatic location for multiple human tumors. In this review, we discuss the immune network in the bone marrow. We suggest that bone marrow is an immune regulatory organ capable of fine tuning immunity and may be a potential therapeutic target for immunotherapy and immune vaccination.

Figure 1

Bone marrow morphology and key cellular components: bone marrow core biopsy sections were subjected to HE staining (a), anti-CD34 staining (b), anti-CD38 staining (c) and anti-CD20 staining (d). The stained sections were revealed with fast red, analyzed by conventional microscope and images were shown with ×40 (a–c) and ×10 (d) magnification. The positive cells were judged by positive staining (red, b–d) as well as the morphology. The control mAb staining reveals no positive cells (not shown). HE, hematoxylin and eosin; mAb, monoclonal antibody.

Figure 2

Bone marrow structure. The bone marrow is encased by cortical bone and traversed by trabecular bone. Bone marrow consists of a highly organized meshwork of thin-walled capillary-venous with extracellaur matrix that fills the space between the bony trabeculae. The artery and the periosteal capillary network are the two sources of arterial blood for the bone marrow. By successive bifurations, small branches of the artery ultimately form the capillary-venous sinus network. Murine and human bone marrow harbor immune cells including Treg cells. T cells including Treg cells may reside in the marrow sinus. Treg, regulatory T.

Figure 3

Molecular and cellular interaction between T cells and marrow sinus: T cells including Treg cells might be in the sinus areas or/and endosteum areas. The organization of molecular and cellular niches is known to have a key role in regulating T-cell immunity. Bone marrow contains a large amount of chemokines, adhesion and integrin molecules. These molecular signals may be important for immune cell bone marrow trafficking, retention and expansion. These structural and molecular niches may play a role in bone pathology in cancer patients with bone metastasis including prostate cancer and breast cancer. BM, bone marrow; CLA, conjugated linoleic acid; DC, dendritic cell; ICAM, intercellular adhesion molecule; LFA, leucocyte function antigen; OB, osteoblast; OC, osteoclast; PSGL, P-selectin glycoprotein ligand; RANKL, receptor activator of NF-kappaB ligand; TGF, transforming growth factor; Treg, regulatory T; VCAM, vascular cell adhesion molecule; VLA, very late antigen.