Chronic obstructive pulmonary disease (COPD) is an inflammatorycondition associated with abnormal immune responses, leading toairflow obstruction. Lungs of COPD subjects show accumulation ofproinflammatory T helper (Th) 1 and Th17 cells resembling that ofautoreactive immune responses. As regulatory T (Treg) cells play acentral role in the control of autoimmune responses and theirgeneration and function are controlled by the adipocytokine lep-tin, we herein investigated the association among systemic leptinoverproduction, reduced engagement of glycolysis in T cells, andreduced peripheral frequency of Tregcells in different COPD stages.These phenomena were also associated with an impaired capacityto generate inducible Treg(iTreg) cells from conventional T (Tconv) cells. At the molecular level, we found that leptin inhibited theexpression of forkhead-boxP3 (FoxP3) and its splicing variants con-taining the exon 2 (FoxP3-E2) that correlated inversely with inflam-mation and weakened lung function during COPD progression. Ourdata reveal that the immunometabolic pathomechanism leading to COPD progression is characterized by leptin overproduction, a de-cline in the expression of FoxP3 splicing forms, and an impairmentin Tregcell generation and function. These results have potentialimplications for better understanding the autoimmune-like natureof COPD and the pathogenic events leading to lung damage.

An immunometabolic pathomechanism for chronic obstructive pulmonary disease / Bruzzaniti, Sara; Bocchino, Marialuisa; Santopaolo, Marianna; Calì, Gaetano; Stanziola, Anna Agnese; D’Amato, Maria; Esposito, Antonella; Barra, Enrica; Garziano, Federica; Micillo, Teresa; Zuchegna, Candida; Romano, Antonella; De Simone, Salvatore; Zuccarelli, Bruno; Mottola, Maria; De Rosa, Veronica; Porcellini, Antonio; Perna, Francesco; Matarese, Giuseppe; Galgani, Mario. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 116:31(2019), pp. 15625-15634. [10.1073/pnas.1906303116]

An immunometabolic pathomechanism for chronic obstructive pulmonary disease

Bocchino, Marialuisa;Santopaolo, Marianna;Stanziola, Anna Agnese;ESPOSITO, ANTONELLA;Garziano, Federica;MICILLO, TERESA;Zuchegna, Candida;Romano, Antonella;Mottola, Maria;De Rosa, Veronica;Porcellini, Antonio;Perna, Francesco;Matarese, Giuseppe
Co-ultimo
;
Galgani, Mario
Co-ultimo
2019

Abstract

Chronic obstructive pulmonary disease (COPD) is an inflammatorycondition associated with abnormal immune responses, leading toairflow obstruction. Lungs of COPD subjects show accumulation ofproinflammatory T helper (Th) 1 and Th17 cells resembling that ofautoreactive immune responses. As regulatory T (Treg) cells play acentral role in the control of autoimmune responses and theirgeneration and function are controlled by the adipocytokine lep-tin, we herein investigated the association among systemic leptinoverproduction, reduced engagement of glycolysis in T cells, andreduced peripheral frequency of Tregcells in different COPD stages.These phenomena were also associated with an impaired capacityto generate inducible Treg(iTreg) cells from conventional T (Tconv) cells. At the molecular level, we found that leptin inhibited theexpression of forkhead-boxP3 (FoxP3) and its splicing variants con-taining the exon 2 (FoxP3-E2) that correlated inversely with inflam-mation and weakened lung function during COPD progression. Ourdata reveal that the immunometabolic pathomechanism leading to COPD progression is characterized by leptin overproduction, a de-cline in the expression of FoxP3 splicing forms, and an impairmentin Tregcell generation and function. These results have potentialimplications for better understanding the autoimmune-like natureof COPD and the pathogenic events leading to lung damage.
2019
An immunometabolic pathomechanism for chronic obstructive pulmonary disease / Bruzzaniti, Sara; Bocchino, Marialuisa; Santopaolo, Marianna; Calì, Gaetano; Stanziola, Anna Agnese; D’Amato, Maria; Esposito, Antonella; Barra, Enrica; Garziano, Federica; Micillo, Teresa; Zuchegna, Candida; Romano, Antonella; De Simone, Salvatore; Zuccarelli, Bruno; Mottola, Maria; De Rosa, Veronica; Porcellini, Antonio; Perna, Francesco; Matarese, Giuseppe; Galgani, Mario. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 116:31(2019), pp. 15625-15634. [10.1073/pnas.1906303116]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/756542
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