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Exercise generates immune cells in bone - Nature.com

Exercise generates immune cells in bone - Nature.com

Exercise generates immune cells in bone - Nature.com
Feb 24, 2021 2 mins, 54 secs

It is pretty crowded in the bone marrow.

Many types of stem and progenitor cell, including progenitors of immune cells, coexist side-by-side1,2 and are supported by nearby cells that generate specialized protective environments for the stem cells, called niches.

The interplay between the cells of the niche, also known as stromal cells, and early progenitors of immune cells in the bone marrow is poorly understood.

The various types of stem and progenitor cell in the bone marrow are highly interconnected, both physically and functionally.

For instance, mesenchymal stem and progenitor cells, which give rise to bone, skeletal tissue and fat cells, are an essential part of the stromal niche for haematopoietic stem and progenitor cells (HSPCs).

In mice, some mesenchymal progenitors produce a signalling protein, called stem cell factor (SCF), that is crucial for supporting HSPCs5.

LepR-expressing (LepR+) cells reside in several distinct locations in bone marrow, including around two types of blood vessel, arterioles and sinusoids.

However, the LepR+ population is a mixture of mesenchymal progenitor cell types5.

They then demonstrated that the cells are short-lived osteogenic progenitors, which give rise to bone-forming cells called osteoblasts that have a crucial role in bone regeneration.

The resulting lack of SCF in Oln+ cells did not affect haematopoietic stem cells or most other types of haematopoietic progenitor cell in the bone marrow.

However, it did lead to a significant reduction in the number of one special type of haematopoietic progenitor — the common lymphoid progenitor (CLP), which gives rise to immune cells called lymphocytes.

In support of the idea that the Oln+ cells help to generate and maintain CLPs, the authors demonstrated that Oln+ cells and CLPs reside close together in the bone marrow.

placed mice in cages that had running wheels, and found that running led to a higher number of both Oln+ cells and CLPs in bone marrow.

The group found that the Oln+ cells express the mechanosensitive ion channel protein Piezo1, and showed that CLP numbers are abnormally low in mice engineered to lack this protein.

Shen et al.3 have identified a population of bone-cell progenitors that resides alongside blood vessels called arterioles in the bone marrow of mice and that expresses the proteins leptin receptor (LepR) and osteolectin (Oln).

Second, it leads to the expression and secretion of a signalling molecule called stem cell factor (SCF), which helps to maintain nearby common lymphoid progenitors (CLPs).

Maintenance of the CLP populations renders them readily able to differentiate into cells of the immune system called lymphocytes that can fight bacterial infections.

Another key question to address will be whether increasing the numbers of Oln+ cells and CLPs in bone marrow would help to provide protection against other disease-causing bacteria, or even viruses, or whether it might also boost vaccination responses.

The authors also found that the number of Oln+ niches, and the number of CLPs, was lower in the bone marrow of 18-month-old mice than in their 2-month-old counterparts.

Mechanosensing is well established to play a part in bone physiology, but a crucial role for mechanosignalling has been also described for other cell types — for instance, pancreatic progenitor cells, intestinal stem cells and the endothelial cells that line blood vessels.

Although less is known about the niches that support stem cells outside the bone marrow, the vasculature, and so endothelial cells, are prime candidates for forming such niches.

It is possible, then, that mechanosensing in niche-forming endothelial cells might contribute to the maintenance of other types of stem and progenitor cell.

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