Skip to main content

REVIEW article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1443297

Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential

Provisionally accepted
Carmen Mazzuca Carmen Mazzuca 1,2*Laura Vitiello Laura Vitiello 3Silvia Travaglini Silvia Travaglini 2Fatima Maurizi Fatima Maurizi 2Panaiotis Finamore Panaiotis Finamore 2Marta Vadacca Marta Vadacca 4Amelia Rigon Amelia Rigon 4Silvia Angeletti Silvia Angeletti 5Simone Scarlata Simone Scarlata 2
  • 1 Allergology Unit, University Hospital Pediatric Department, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy
  • 2 Unit of Internal Medicine and Geriatrics, Respiratory Pathophysiology and Thoracic Endoscopy, Fondazione Policlinico Campus Bio Medico University Hospital, Rome, Italy
  • 3 Laboratory of Flow Cytometry, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele, Rome, Italy
  • 4 Unit of Allergology, Immunology, Rheumatology, Department of Medicine, University Campus Bio-Medico di Roma, Rome, Sicily, Italy
  • 5 Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy

The final, formatted version of the article will be published soon.

    α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

    Keywords: serine protease inhibitor superfamily (SERPIN), anti-inflammation, autoimmune disease, infectious disease, Severe Acute Respiratory Syndrome COronaVirus2 (SARS-CoV-2) reactive oxygen species, NETs: neutrophils extracellular traps, sIC: soluble immunocomplexes, PBMCs peripheral blood mononuclear cells: DCs: dendritic cells, LTB4: leukotriene B4, TMPRSS2: transmembrane serine protease 2, ACPA: anticitrullinated peptide Commentato [CM2]: New affiliation Commentato [CM3]: Reviewer 3-Q1 Commentato [CM4]: Reviewer 3-Q1 Commentato [CM5]: Reviewer 2 Commentato [CM6]: Reviewer 2 Commentato [CM7]: Reviewer 2 Commentato [CM8]: Reviewer 3-Q1

    Received: 03 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Mazzuca, Vitiello, Travaglini, Maurizi, Finamore, Vadacca, Rigon, Angeletti and Scarlata. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Carmen Mazzuca, Allergology Unit, University Hospital Pediatric Department, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.