title: Human TH17 cells are long-lived effector memory cells.
abstract: T helper 17 (TH17) cells have been shown to contribute to multiple disease systems. However, the functional phenotype and survival pattern of TH17 cells as well as the underlying mechanisms that control TH17 cells have been poorly investigated in humans, significantly hampering the clinical targeting of these cells. Here, we studied human TH17 cells in the pathological microenvironments of graft-versus-host disease, ulcerative colitis, and cancer; TH17 cell numbers were increased in the chronic phase of these diseases. Human TH17 cells phenotypically resembled terminally differentiated memory T cells but were distinct from central memory, exhausted, and senescent T cells. Despite their phenotypic markers of terminal differentiation, TH17 cells mediated and promoted long-term antitumor immunity in in vivo adoptive transfer experiments. Furthermore, TH17 cells had a high capacity for proliferative self-renewal, potent persistence, and apoptotic resistance in vivo, as well as plasticity-converting into other types of TH cells. These cells expressed a relatively specific gene signature including abundant antiapoptotic genes. We found that hypoxia-inducible factor-1α and Notch collaboratively controlled key antiapoptosis Bcl-2 family gene expression and function in TH17 cells. Together, these data indicate that human TH17 cells may be a long-lived proliferating effector memory T cell population with unique genetic and functional characteristics. Targeting TH17-associated signaling pathway would be therapeutically meaningful for treating patients with autoimmune disease and advanced tumor.
authors: Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Ilona
authors: I
authors: Kryczek
authors: Ende
authors: E
authors: Zhao
authors: Yan
authors: Y
authors: Liu
authors: Yin
authors: Y
authors: Wang
authors: Linhua
authors: L
authors: Vatan
authors: Wojciech
authors: W
authors: Szeliga
authors: Jeffrey
authors: J
authors: Moyer
authors: Aleksandra
authors: A
authors: Klimczak
authors: Andrzej
authors: A
authors: Lange
authors: Weiping
authors: W
authors: Zou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007156:Immunologic Memory; D051379:Mice; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051880:Receptors, Notch