CD1d-dependent NKT cells play a protective role in acute and chronic arthritis models by ameliorating antigen-specific Th1 responses

A Teige, R Bockermann, M Hasan… - The Journal of …, 2010 - journals.aai.org
A Teige, R Bockermann, M Hasan, KE Olofsson, Y Liu, S Issazadeh-Navikas
The Journal of Immunology, 2010journals.aai.org
A protective and anti-inflammatory role for CD1d-dependent NKT cells (NKTs) has been
reported in experimental and human autoimmune diseases. However, their role in arthritis
has been unclear, with conflicting reports of CD1d-dependent NKTs acting both as
regulatory and disease-promoting cells in arthritis. These differing modes of action might be
due to genetic differences of inbred mice and incomplete backcrossing of gene-modified
mice. We therefore put special emphasis on controlling the genetic backgrounds of the mice …
Abstract
A protective and anti-inflammatory role for CD1d-dependent NKT cells (NKTs) has been reported in experimental and human autoimmune diseases. However, their role in arthritis has been unclear, with conflicting reports of CD1d-dependent NKTs acting both as regulatory and disease-promoting cells in arthritis. These differing modes of action might be due to genetic differences of inbred mice and incomplete backcrossing of gene-modified mice. We therefore put special emphasis on controlling the genetic backgrounds of the mice used. Additionally, we used two different murine arthritis models, Ag-induced arthritis (AIA) and collagen-induced arthritis (CIA), to evaluate acute and chronic arthritis in CD1d knockout mice and mice depleted of NK1. 1+ cells. CD1d-deficient mice developed more severe AIA compared with wild-type littermates, with a higher degree of inflammation and proteoglycan depletion. Chronic arthritis in CIA was also worse in the absence of CD1d-dependent NKTs. Elevated levels of Ag-specific IFN-γ production accompanied these findings rather than changes in IL-17α. Depletion of NK1. 1+ cells supported these findings in AIA and CIA. This report provides support for CD1d-dependent NKTs being suppressor cells in acute and chronic arthritis, likely via inhibition of arthritogenic Th1 cells. These results make CD1d-dependent NKTs an attractive target for therapeutic intervention.
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