SOCS3: a new target for anti-allergy drugs

Suppressor of cytokine signalling (SOCS) proteins, due to their action as negative regulators of cytokine signalling, are implicated in the pathogenesis of numerous inflammatory diseases. Cytokines secreted by T helper 2 (T_H2) cells are central to the development of allergic disease — what role do SOCS proteins have in this setting? Here, Seki et al. show that SOCS3, which is mainly expressed by T_H2 cells, regulates the onset and maintenance of T_H2-cell-mediated allergic responses.

First, Seki et al. studied the expression patterns of SOCS3 in patients with atopic asthma or dermatitis compared with healthy people. Expression of SOCS3 by peripheral T cells correlated with the severity of disease — the more severe the disease pathology, the higher the level of SOCS3 expression by T cells from those individuals. Serum immunoglobulin E levels, which have been implicated in the pathogenesis of allergic disease, were also increased in individuals with high SOCS3 expression. The authors concluded that the increased levels of SOCS3 reflected an accumulation of T_H2 cells in patients with allergic inflammatory disease and were associated with increased disease pathology.

To investigate the functional relevance of SOCS3 overexpression, the authors generated transgenic mice in which T cells constitutively expressed Socs3. The differentiation of CD4⁺ T cells into interleukin-4-producing T_H2 cells was enhanced in these mice. Using an ovalbumin-induced asthma model, the authors showed that airway hyper-responsiveness was markedly higher in the Socs3-transgenic mice, as were the levels of IgE, T_H2 cytokines and eosinophils in the bronchoalveolar lavage fluids, compared with control mice. These results indicate that elevated expression of SOCS3 by T cells results in enhanced T_H2-cell responses, which contributes to the onset and development of asthmatic disease.

Finally, Seki et al. studied Socs3^+/− mice and transgenic mice expressing a dominant-negative Socs3 protein in their T cells to see what effect interfering with the expression of Socs3 would have on T_H2-cell development. As expected, reduced Socs3 activity resulted in suppressed T_H2-cell development in these models.

So, as the authors state, “SOCS3 expression in T cells could be an important diagnostic marker of T_H2-type diseases, as well as a candidate for therapeutic targeting of these diseases”.