Pulmonary arterial hypertension (PAH) encompasses a group of conditions with distinct causes. Dysimmunity is a common feature of all forms of PAH and contributes to both disease susceptibility and/or progression. Regulatory T lymphocytes (Treg) are dysfunctional in idiopathic PAH (iPAH) patients in a leptin-dependent manner. However, it is not known whether these abnormalities are specific to iPAH. Hence, we hypothesized that (1) Treg dysfunction is also present in heritable (hPAH) and connective tissue disease-associated PAH (CTD-PAH); (2) defective leptin-dependent signaling is present in hPAH and CTD-PAH and could contribute to Treg dysfunction; (3) modulating leptin axis in vivo could protect against Treg dysfunction; (4) restoration of Treg activity could limit and/or reverse experimental chronic hypoxia (Hx)-induced pulmonary hypertension (PH) in vivo. We analysed 62 patients with PAH (30 iPAH, 18 hPAH and 14 CTD-PAH), 10 CTD patients without PAH and 20 healthy controls. Our results indicate that Treg are dysfunctional in all PAH forms tested, as well as in CTD patients without PAH. Importantly, leptin axis is crucial in Treg dysfunction in iPAH and CTD patients (with or without PAH), whereas in hPAH, Treg are altered in a leptin independent manner. Using leptin receptor (ObR)-deficient rats which develop less severe Hx-PH, we found that ObR-deficient rats are protected against decreased Treg function after Hx exposure. Taken altogether, our results suggest that Treg dysfunction is common to all forms of PAH and may contribute to the development and/or the progression of the disease.