Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential Counter-Regulatory Effect in Primary Sjögren's Syndrome.

Gábor Papp,Margit Zeher,Edit Gyimesi,Krisztina Szabó,Éva Zöld

doi:10.1155/2016/4328372

Abstract

Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19+CD5+ and CD19+CD5− B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19+CD24highCD38high), mature (CD19+CD24intCD38int) and primarily memory (CD19+CD24highCD38−) B cells. CD5+ but not CD5− B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19+ B cells. Our results suggest that enhanced IL-21R expression of CD19+CD5+ B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19+CD5+ B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.

Highlights

Primary Sjogren’s syndrome is a common systemic autoimmune disease characterized by inflammation and consequential destruction of exocrine glands
We investigated the expression of IL-21 receptor (IL-21R) and granzyme B (GrB) of B cell subsets; we assessed the IL-21 expression of invariant natural killer T (iNKT) cells and determined the distribution of transitional, mature, and primarily memory B cell subsets in the peripheral blood of Primary Sjogren’s syndrome (pSS) patients
When GrB expressions of these B cell subsets were investigated, in the whole CD19+ B cell population, significantly enhanced GrB expression was observed in the whole group of pSS patients (median: 5.225 (0.41–28.1)% versus 3.69 (0.04–7.29)%, resp., p = 0.0121) and in all subgroups of patients (pSS glandular: median: 5.505 (0.41–28.1)% versus 3.69 (0.04– 7.29)%, resp., p = 0.0261; pSS extraglandular manifestations (EGMs): median: 4.735 (0.73–22.34)% versus 3.69 (0.04–7.29)%, resp., p = 0.0486), compared to the values measured in the healthy controls (Figure 1)

Summary

Introduction

Primary Sjogren’s syndrome (pSS) is a common systemic autoimmune disease characterized by inflammation and consequential destruction of exocrine glands. The pathological hallmark of pSS is extensive lymphocytic infiltration in salivary glands. The extension and structural arrangement of the infiltrations vary between wide limits; even ectopic germinal centres may develop. These structures are characterized by in situ autoantibody production and high expression of homing and retentive chemokines and adhesion molecules. It was reported that the number of ectopic GCs in salivary glands correlates with the severity of inflammation and anti-SSA/SSB autoantibody production [1, 2]. Formation of ectopic GCs in glandular tissues carries a higher risk of developing B cell lymphoma in pSS [3]

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