Drs. Hirofumi Amano and Eri Amano contributed equally to this work.
Selective expansion of a monocyte subset expressing the CD11c dendritic cell marker in the Yaa model of systemic lupus erythematosus
Article first published online: 2 SEP 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 9, pages 2790–2798, September 2005
How to Cite
Amano, H., Amano, E., Santiago-Raber, M.-L., Moll, T., Martinez-Soria, E., Fossati-Jimack, L., Iwamoto, M., Rozzo, S. J., Kotzin, B. L. and Izui, S. (2005), Selective expansion of a monocyte subset expressing the CD11c dendritic cell marker in the Yaa model of systemic lupus erythematosus. Arthritis & Rheumatism, 52: 2790–2798. doi: 10.1002/art.21365
- Issue published online: 2 SEP 2005
- Article first published online: 2 SEP 2005
- Manuscript Accepted: 31 MAY 2005
- Manuscript Received: 23 MAR 2005
- Swiss National Foundation for Scientific Research
- NIH. Grant Number: AR-37070
Monocytosis is a unique cellular abnormality associated with the Yaa (Y-linked autoimmune acceleration) mutation. The present study was designed to define the cellular mechanism responsible for the development of monocytosis and to characterize the effect of the Yaa mutation on the development of monocyte subsets.
We produced bone marrow chimeras reconstituted with a mixture of Yaa and non-Yaa bone marrow cells bearing distinct Ly-17 alloantigens, and determined whether monocytes of Yaa origin became dominant. Moreover, we defined the 2 major inflammatory (Gr-1+,CD62 ligand [CD62L]+) and resident (Gr-1−,CD62L−) subsets of blood monocytes in aged BXSB Yaa male mice, as compared with BXSB male mice lacking the Yaa mutation.
Analysis of the Ly17 allotype of blood monocytes in chimeric mice revealed that monocytes of both Yaa and non-Yaa origin were similarly involved in monocytosis. Significantly, the development of monocytosis paralleled a selective expansion of the resident monocyte subset compared with the inflammatory subset, and the former expressed CD11c, a marker of dendritic cells. Neither monocytosis nor the change in monocyte subpopulations, including CD11c expression, was observed in Yaa-bearing C57BL/6 mice, in which systemic lupus erythematosus (SLE) fails to develop.
Our results suggest that Yaa-associated monocytosis is not attributable to an intrinsic abnormality in the growth potential of monocyte lineage cells bearing the Yaa mutation and that the Yaa mutation could lead to the expansion of dendritic cells, thereby contributing to the accelerated development of SLE.