Glucocorticoid Resistance of Th17 Cells in Takayasu Arteritis

Glucocorticoid Resistance of Th17 Cells in Takayasu Arteritis

A study published in the Arthritis & Rheumatology journal is perhaps the first to demonstrate that T helper (Th)1 and Th17 cells and cytokine pathways may play central role in driving systemic inflammation in Takayasu arteritis.

The first case of Takayasu’s arteritis was described in 1908 by Dr. Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society. Dr. Takayasu described a peculiar “wreathlike” appearance of blood vessels in the back of the eye (retina).

Takayasu arteritis (TA) is a rare type of vasculitis that affects mostly middle-aged women, with greater frequency in Asia, South America and the Mediterranean countries.

It is characterized by a granulomatous inflammation of the aorta and its major branches, and is associated with high cellular infiltrates including T helper and cytotoxic T cells, macrophages and neutrophils.

Glucocorticoids (GCs) are anchor drugs for this disease and few previous studies raised the possibility that Th1 and Th17 cells may be involved in the pathogenesis of Takayasu arteritis (Chikashi Terao et al., 2014).

However, the nature and type of T cells driving inflammation in TA and how GCs affect different components of cellular immunity in this condition remain largely unknown.

In the study published in the Arthritis & Rheumatology, David Saadoun and colleagues from the Pierre and Marie Curie University, Paris, France evaluated 41 patients under the American College of Rheumatology criteria for TA.

The authors report that Th1- and Th17-related cytokines are increased in TA patients and correlate with disease activity.

The immunohistochemical analysis of vascular infiltrates revealed the presence of IFN-γ, IL-6 and IL-17A producing cells. Of note, when serum from active TA patients was added to CD4+ T cells culture of healthy donors, an increased production of IL-17 and IFN-γ was observed.

Importantly, the study also showed that TA patients under GCs therapy had decreased circulating Th1-related cytokines such as TNF-α, IL-2 and IFN-γ.

However, the inhibitory effect of GCs spared Th17-related cytokines, corroborating previous studies that point out the glucocorticoid resistance of Th17 cells as a hallmark of the pathogenic, pro-inflammatory nature of these cells.

Thus, the Saadoun et al. study may also indicate that therapies aimed at Th17 cells should be considered for optimal control of Takayasu arteritis.

Source: Arthritis & Rheumatology, 2014. Accepted manuscript.doi: 10.1002/art.39037
Read more: Arthritis & Rheumatology

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Cover Image Credit: Johns Hopkins Vasculitis Center, A normal aortic arch on the left, with narrow, smooth blood vessels. On the right is an example of an abnormal aortic arch in a patient with Takayasu’s, with obvious dilation of the ascending aorta on the left side of the picture.