Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response

Abstract Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining, we hypothesized that Chinese medicine formula Yu-Ping-Feng might be a promising candidate for treating primary Sjögren syndrome, a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren syndrome that we previously established for Yu-Ping-Feng formula treatment. Yu-Ping-Feng therapy ameliorated the experimental Sjögren syndrome pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using coculture assay and adoptive transfer models, we demonstrated that Yu-Ping-Feng formula directly restrained effector/memory T-cell expansion and differentiation into Th17 and T follicular helper cells, the key subsets in experimental Sjögren syndrome pathogenesis. Importantly, we recruited 20 patients with primary Sjögren syndrome and conducted a pilot study of 8-wk therapy of Yu-Ping-Feng formula. Yu-Ping-Feng treatment effectively improved fatigue symptoms and exocrine gland functions, as well as reduced serum IgG/IgA levels, while effector T- and B-cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggest a novel approach to assess the immunomodulatory effects of Yu-Ping-Feng formula, which may be favorable for patients with autoimmune disorders.