title: Th17 immune responses contribute to the pathophysiology of aplastic anemia.
abstract: T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3(+)CD4(+)IL-17-producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4(+)CD25(high)FoxP3(+) regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4(+) and CD8(+) IL-17-producing T cells in a mouse model of lymph node infusion-induced BM failure. Although anti-IL-17 treatment did not abrogate BM failure, early treatment with the anti-IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression.
authors: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. peffaultdelatour@sls.aphp.fr
authors: Regis Peffault
authors: RP
authors: de Latour
authors: Valeria
authors: V
authors: Visconte
authors: Tomoiku
authors: T
authors: Takaku
authors: Colin
authors: C
authors: Wu
authors: Andrew J
authors: AJ
authors: Erie
authors: Annahita K
authors: AK
authors: Sarcon
authors: Marie J
authors: MJ
authors: Desierto
authors: Phillip
authors: P
authors: Scheinberg
authors: Keyvan
authors: K
authors: Keyvanfar
authors: Olga
authors: O
authors: Nunez
authors: Jichun
authors: J
authors: Chen
authors: Neal S
authors: NS
authors: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003710:Demography; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D007371:Interferon-gamma