title: Interleukin 21 correlates with T cell and B cell subset alterations in systemic lupus erythematosus.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by alterations of the B cell subset, global regulatory T cell (Treg) depletion, and an increase in Th17 cells. Interleukin 21 (IL-21) plays a critical role in T cell and B cell homeostasis. Our objective was to determine the implication of IL-21 and IL-21-producing CD4+ T cells in the pathogenesis of SLE.
  
  
  METHODS
  Twenty-five patients with SLE and 25 healthy donor controls were included. Analysis of CD4+ T cells producing IL-21, Th1, Th2, Th17, Treg, follicular helper T (TFH) cells, and B cells was performed in peripheral blood, and levels of cytokines were measured in culture supernatants.
  
  
  RESULTS
  Circulating CD4+ T cells producing IL-21 were markedly expanded in patients with SLE compared to controls and were correlated with increased Th17, decreased Treg, and increased memory B cells. CD4+ T cells producing IL-21 were composed of CXCR5+ and CXCR5-CD4+ T cell subsets. Both IL-21-producing CXCR5+CD4+ T cells and CXCR5-CD4+ T cells were increased in patients with SLE, the CXCR5-CD4+ subset correlating with Th17 cells and Treg, while the CXCR5+CD4+ subset was correlated with alterations of the B cell subset. The CXCR5+CD4+ subset comprised mainly circulating Bcl6+CXCR5+CD4+ TFH cells that were markedly expanded in patients with SLE and were correlated with increased circulating Bcl6+CXCR5+ germinal center B cells.
  
  
  CONCLUSIONS
  These findings suggest that IL-21, produced by distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell subsets in SLE, and that targeting IL-21 could provide beneficial effects on both T cell and B cell alterations.
authors.affiliation: UPMC Université Paris, CNRS, UMR 7211, INSERM, UMRS959, and Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, 47 boulevard de l'Hôpital, 75013 Paris, France. benj.terrier@gmail.com
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.forename: Marlène
authors.initials: M
authors.lastname: Garrido
authors.forename: Guillaume
authors.initials: G
authors.lastname: Geri
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21