Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of collagen-induced arthritis

Abstract

IFT20 is the smallest member of the intraflagellar transport protein (IFT) complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20 ^flox/flox (IFT20 ^f/f ) mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis (CIA). We found that both Lck-Cre/IFT20 ^f/f and CD4-Cre/IFT20 ^f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20 ^f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20 ^f/f mice compared to Lck-Cre/IFT20 ^+/+ littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20 ^f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1β, IL-6 and TGF-β1 were significantly downregulated in the paw of Lck-Cre/IFT20 ^f/f mice, but just slight decreased in CD4-Cre/IFT20 ^f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

Arthritis: Understanding the role of T-cells

The severity of arthritis in mice is reduced by deletion of a protein in early stage T-cell differentiation. T-cells, a type of white blood cell, are known to mediate arthritis; however, the processes governing T-cell behavior in arthritis are unclear. Shuying Yang and co-workers at the University at Buffalo, SUNY have uncovered the complex role of IFT20 in T-cell differentiation by studying mice with collagen-induced arthritis (CIA). The team created two CIA mouse models: one model with IFT20 deletion at early stage T-cell differentiation, and a second model with deletion in mature T-cells. Loss of IFT20 led to a significant reduction in CIA symptoms in the first model, but not the second. The team concluded that IFT20 is an important regulator of T-cell differentiation, but does not noticeably affect mature T-cells.

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