Mouse CD163 deficiency strongly enhances experimental collagen-induced arthritis

Pia Svendsen,Anders Etzerodt,Bent W Deleuran,Søren K Moestrup

doi:10.1038/s41598-020-69018-7

Abstract

The scavenger receptor CD163 is highly expressed in macrophages in sites of chronic inflammation where it has a not yet defined role. Here we have investigated development of collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) in CD163-deficient C57BL/6 mice. Compared to wild-type mice, the CIA in CD163-deficient mice had a several-fold higher arthritis score with early onset, prolonged disease and strongly enhanced progression. Further, the serum anti-collagen antibody isotypes as well as the cytokine profiles and T cell markers in the inflamed joints revealed that CD163-deficient mice after 52 days had a predominant Th2 response in opposition to a predominant Th1 response in CD163+/+ mice. Less difference in disease severity between the CD163+/+ and CD163−/− mice was seen in the CAIA model that to a large extent induces arthritis independently of T-cell response and endogenous Th1/Th2 balance. In conclusion, the present set of data points on a novel strong anti-inflammatory role of CD163.

Highlights

The scavenger receptor CD163 is highly expressed in macrophages in sites of chronic inflammation where it has a not yet defined role
We observed a much more severe development of collagen-induced arthritis (CIA) in C57BL/6 mice deficient in CD163 expression compared to wild-type C57BL/6 mice that have a genetic background characterized by a general low susceptibility to collagen immunization in terms of arthritis development
A similar difference was not seen in the collagen antibody-induced arthritis (CAIA) model, wherein arthritis was induced with collagen antibodies directly

Summary

Introduction

The scavenger receptor CD163 is highly expressed in macrophages in sites of chronic inflammation where it has a not yet defined role. Less difference in disease severity between the CD163+/+ and CD163−/− mice was seen in the CAIA model that to a large extent induces arthritis independently of T-cell response and endogenous Th1/Th2 balance. The receptor and its function have been most intensively studied in human systems, but the selective myelomonocytic expression of CD163 with a high upregulation in the M2-type macrophages is seen in animals including rodents[2,3]. In many chronic inflammatory diseases, such as rheumatoid arthritis (RA), CD163 is highly up-regulated[5,11] at the sites inflammation, which is in line with clinical e vidence[12] showing that accumulation of M2-type macrophages is an important part of the chronic and late inflammatory response. Polarization rather than an exact description of the many overlapping classes of macrophages and their role in inflammation in vivo and the use of the nomenclature is much debated[16]

Methods

Results

Conclusion