6533b834fe1ef96bd129cda6

RESEARCH PRODUCT

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.

Patrick ManckoundiaJean Francis MaillefertLuc MouthonMalika TradLaurent MartinJennifer FraszczakSylvain AudiaNicolas LarmonierJulien VinitPhilippe SaasMarion CiudadBernard BonnotteSerge Aho-gléléJean François BesancenotV. LeguyDaniela LakomyNona JanikashviliLoïc GuillevinSabine BerthierBernard LorcerieMaxime SamsonNils Olivier OlssonAndrew BatemanPaul Ornetti

subject

MalePathologyMESH: Th17 CellsCellMESH : AgedMESH : Prospective StudiesMESH: Flow CytometryT-Lymphocytes RegulatoryPathogenesisMESH : T-Lymphocytes Regulatory0302 clinical medicineimmune system diseasesMESH : Th1 CellsImmunology and Allergy[ SDV.IMM ] Life Sciences [q-bio]/ImmunologyPharmacology (medical)MESH : FemaleProspective Studiesskin and connective tissue diseasesCells CulturedMESH: Aged0303 health sciencesMESH: Middle Agedmedicine.diagnostic_testMESH: Giant Cell ArteritisCell DifferentiationMESH : AdultMiddle AgedFlow CytometryMESH : NK Cell Lectin-Like Receptor Subfamily B3. Good healthMESH: NK Cell Lectin-Like Receptor Subfamily Bmedicine.anatomical_structure[SDV.IMM]Life Sciences [q-bio]/ImmunologyFemaleVasculitisMESH : Cell DifferentiationGlucocorticoidmedicine.drugNK Cell Lectin-Like Receptor Subfamily BMESH: Cells CulturedAdultMESH: Cell Differentiationmedicine.medical_specialty[SDV.IMM] Life Sciences [q-bio]/ImmunologyMESH : Flow CytometryT cellMESH : MaleImmunologyGiant Cell ArteritisBiologyPolymyalgia rheumatica03 medical and health sciencesRheumatologyBiopsyMESH : Cells CulturedmedicineMESH : Th17 CellsHumansMESH : Middle Aged030304 developmental biologyAged030203 arthritis & rheumatologyMESH: HumansMESH: T-Lymphocytes RegulatoryMESH : HumansMESH: AdultTh1 Cellsmedicine.diseaseMESH : Giant Cell ArteritisMESH: Prospective StudiesMESH: MaleGiant cell arteritisMESH: Th1 CellsPolymyalgia RheumaticaMESH: Polymyalgia RheumaticaImmunologyTh17 CellsMESH : Polymyalgia RheumaticaMESH: Female

description

International audience; OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.

10.1002/art.34647https://www.hal.inserm.fr/inserm-00799573