AUTHOR=Grados Aurélie , Ebbo Mikael , Piperoglou Christelle , Groh Matthieu , Regent Alexis , Samson Maxime , Terrier Benjamin , Loundou Anderson , Morel Nathalie , Audia Sylvain , Maurier François , Graveleau Julie , Hamidou Mohamed , Forestier Amandine , Palat Sylvain , Bernit Emmanuelle , Bonotte Bernard , Farnarier Catherine , Harlé Jean-Robert , Costedoat-Chalumeau Nathalie , Vély Frédéric , Schleinitz Nicolas 

TITLE=T Cell Polarization toward TH2/TFH2 and TH17/TFH17 in Patients with IgG4-Related Disease

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00235

DOI=10.3389/fimmu.2017.00235

ISSN=1664-3224

ABSTRACT=<p>IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease’s pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes’ subsets were analyzed by flow cytometry, with analysis of T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17, T<sub>FH</sub> cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren’s syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T<sub>H</sub>2, T<sub>H</sub>17, and CD4<sup>+</sup>CXCR5<sup>+</sup>PD1<sup>+</sup> T<sub>FH</sub> cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. T<sub>FH</sub> increase was characterized by the specific expansion of T<sub>FH</sub>2 (CCR6<sup>−</sup>CXCR3<sup>−</sup>), and to a lesser extent of T<sub>FH</sub>17 (CCR6<sup>+</sup>CXCR3<sup>−</sup>) cells. Interestingly, CD4<sup>+</sup>CXCR5<sup>+</sup>PD1<sup>+</sup> T<sub>FH</sub> cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T<sub>H</sub>2/T<sub>FH</sub>2 and T<sub>H</sub>17/T<sub>FH</sub>17 polarization. This immunological imbalance might be implicated in the disease’s pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.</p>