Clinical relevance of RORγ positive and negative subsets of CD161+CD4+ T cells in primary Sjögren's syndrome.
The relevance of the Th17 pathway in primary SS (pSS) is unclear. Published studies have relied on restimulating circulating CD161+T cells in vitro for quantitation of IL-17-producing cells. While CD161 marks all IL-17+T cells, it is also expressed by other Th subsets. The aim of this study was to directly analyse retinoic acid receptor-related orphan nuclear receptor (ROR)-γ expressing and non-expressing subsets of CD161+T cells to determine the relevance of the Th17 pathway in pSS.



We quantitated the frequencies of both CD161-and RORγ-expressing T cells by comparative flow cytometry in peripheral blood mononuclear cells from a well-stratified cohort of pSS patients and control subjects. We also analysed the expression of antigen D-related HLA (HLA-DR) and CD161 in labial salivary glands from nine subjects undergoing a diagnostic biopsy.



While the frequencies of both RORγ+and RORγ-subsets of CD161+CD4+T cells were increased in peripheral blood from pSS patients, the increase in the RORγ+subset positively correlated with humoral manifestations of the disease (anti-SSA/SSB autoantibodies and hypergammaglobulinaemia), but not with disease activity, and vice versa for the RORγ-subset. An increased frequency of HLA-DR+CD161+CD4+T cells was observed in labial salivary gland biopsies from pSS patients, suggesting chronic activation of CD161+CD4+T cells in the target tissue of the disease.



In addition to pointing to CD161 as a marker of a pathogenic subset of CD4+T cells in pSS patients, our data indicate that even though the RORγ+(Th17) CD161+subset might contribute to humoral manifestations of the disease, the RORγ-(non-Th17) CD161+subset is the one associated with disease activity in pSS patients.
Immunology Research, Biogen, Cambridge, MA, USA.
Linlin
L
Zhao
Faculté de Médecine, Université Paris Sud.|INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases.|Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France.
Gaetane
G
Nocturne
Immunology Research, Biogen, Cambridge, MA, USA.
Scott
S
Haskett
Faculté de Médecine, Université Paris Sud.|INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases.
Saida
S
Boudaoud
Faculté de Médecine, Université Paris Sud.|INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases.|Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France.
Thierry
T
Lazure
Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France.
Christine
C
Le Pajolec
Faculté de Médecine, Université Paris Sud.|INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases.|Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France.
Xavier
X
Mariette
Immunology Research, Biogen, Cambridge, MA, USA.
Michael
M
Mingueneau
Immunology Research, Biogen, Cambridge, MA, USA daliya.banerjee@gmail.com.
Daliya
D
Banerjee
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
D000974:Antibodies, Antinuclear; D006684:HLA-DR Antigens; D055651:NK Cell Lectin-Like Receptor Subfamily B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; C035356:SS-A antibodies; C035357:SS-B antibodies
CD161; RORγ/gamma; Th17; primary Sjögren’s syndrome; salivary gland biopsy