title: Autoreactive Th1 cells activate monocytes to support regional Th17 responses in inflammatory arthritis.
abstract: We have examined mechanisms underlying the formation of pathologic Th17 cells using a transgenic mouse model in which autoreactive CD4(+) T cells recognize influenza virus hemagglutinin (HA) as a ubiquitously expressed self-Ag and induce inflammatory arthritis. The lymph nodes of arthritic mice contain elevated numbers of inflammatory monocytes (iMO) with an enhanced capacity to promote CD4(+) Th17 cell differentiation, and a regional inflammatory response develops in the paw-draining lymph nodes by an IL-17-dependent mechanism. The activation of these Th17-trophic iMO precedes arthritis development and occurs in the context of an autoreactive CD4(+) Th1 cell response. Adoptive transfer of HA-specific CD4(+) T cells into nonarthritic mice expressing HA as a self-Ag similarly led to the formation of Th1 cells and of iMO that could support Th17 cell formation, and, notably, the accumulation of these iMO in the lymph nodes was blocked by IFN-γ neutralization. These studies show that autoreactive CD4(+) Th1 cells directed to a systemically distributed self-Ag can promote the development of a regional Th17 cell inflammatory response by driving the recruitment of Th17-trophic iMO to the lymph nodes.
authors: The Wistar Institute, Philadelphia, PA 19104, USA.
authors: Donald M
authors: DM
authors: Simons
authors: Soyoung
authors: S
authors: Oh
authors: Elizabeth
authors: E
authors: Kropf
authors: Malinda
authors: M
authors: Aitken
authors: Victoria
authors: V
authors: Garcia
authors: Alissa
authors: A
authors: Basehoar
authors: Andrew J
authors: AJ
authors: Caton
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D001324:Autoantigens; D016207:Cytokines; D007371:Interferon-gamma