title: γδT Cell-derived interleukin-17A via an interleukin-1β-dependent mechanism mediates cardiac injury and fibrosis in hypertension.
abstract: Inflammation is implicated in the initiation of hypertension and end-organ injury. Interleukin-17A (IL-17A) is a key pathogenic factor in a variety of inflammatory diseases and hypertension. However, the mechanisms underlying IL-17A production, and its role in mediating inflammation and early cardiovascular injury in hypertensive heart, remain unknown. Angiotensin II (Ang II) infusion increased cardiac IL-17A mRNA expression and IL-17A+CD3+ cell infiltration in a time-dependent manner. IL-17A in the hypertensive heart was derived mostly from infiltrating γδT cells rather than from CD4 T cells. Genetic knockdown of γδT cells or specific anti-γδT antibody abolished IL-17A production in Ang II–infused heart. Moreover, monocyte-secreted IL-1β, not cardiac fibroblast–secreted IL-6 or transforming growth factor-β, was required for IL-17A production from γδT cell. IL-17A accelerated differentiation of myofibroblast through promoting IL-6 production from cardiac fibroblast. Finally, inflammatory cell infiltration, proinflammatory or profibrotic cytokine expression, and fibrotic lesion induced by Ang II were attenuated in IL-17A–deficient mice. Moreover, the deletion of γδT cell was protected from Ang II–induced cardiac injury. Thus, a triangular positive feedback loop exists among monocytic-secreted IL-1β, γδT-cell–derived IL-17A, and cardiac fibroblast–produced IL-6, which triggers the cardiac injury in hypertension.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Yina
authors.initials: Y
authors.lastname: Wu
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Jianlei
authors.initials: J
authors.lastname: Hao
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000804:Angiotensin II; D000818:Animals; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D000804:Angiotensin II