Constitutive STAT3 activation in peripheral CD3⁺ cells from patients with primary Sjögren's syndrome

Abstract

Objective: Signal transducers and activators of transcription (STATs) are crucial mediators of cytokine signalling. Constitutive activation of STATs, especially STAT3, has been reported in several diseases. Primary Sjögren's syndrome (pSS) is associated with overproduction of cytokines such as interleukin‐10 (IL‐10), although the mechanism by which this occurs is unknown. As STAT3 is a potent inducer of IL‐10, this study focused on determining the pattern of STAT3 activation in peripheral lymphocytes from patients with pSS.

Methods: Twelve pSS patients and 12 healthy age‐matched control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation. Phosphorylated STAT3 (pSTAT3) and also STAT3 expression were determined by flow cytometry in gated CD3⁺ and CD19⁺ lymphocytes. Similarly, pJak1 and pTyk2 were also determined in gated CD3⁺ lymphocytes.

Results: Although the protein expression of STAT3 was similar among controls and pSS patients, we found that STAT3 was constitutively activated in CD3⁺ lymphocytes from pSS patients. Neither Jak1 nor Tyk2 (the upstream activators of STAT3) was activated in pSS CD3⁺ lymphocytes, suggesting that the constitutive activation of STAT3 observed in pSS patients might not depend on cytokine stimulation but instead might be the result of an abnormal inactivation of pSTAT3.

Conclusions: These data provide evidence of abnormal STAT3 signalling in T cells from pSS patients.