Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types

Abstract

Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.

Keywords:

• Nurse-like cell
• survival niche
• synovial tissue
• bone marrow
• rheumatoid arthritis

Acknowledgments

The authors are grateful for the great collaboration and support of the people listed in each paper related to this review. The authors appreciate Technical Support Center for Life Science Research (LSR) Iwate Medical University in skillful techniques of electron microscopy, especially 3D analysis of nursing phenomenon. The authors are grateful to Ms K. Tashiro for assisting making a manuscript.

Conflict of interest

None.

Additional information

Funding

This work was supported in part by a grant-in-aid from the Health Science Research grant from the Ministry of Health and Welfare of Japan to TO, and grants-in-aid for scientific research from the Japan Society for the Promotion of Science [No. 15K10421] and the Nakatomi Foundation Grant to KO.