**1. Introduction**

The primary physiological function of heme oxygenase (HO), a rate-limiting enzyme in heme metabolism, is to degrade heme into biliverdin (BV), free ferrous ion (Fe2+), and carbon monoxide (CO). BV is converted to bilirubin (BR), and iron is sequestered into ferritin. HO has two main isoforms, HO-1 and HO-2, of which HO-1 is an inducible isoform with molecular weight 32-kD. HO-1 is considered a protective protein. HO-1 is encoded by HMOX1 and regulated transcriptionally. HO-1 is expressed at low levels or is absent in most tissues except the spleen and liver under homeostatic conditions and highly expressed in response to various stimuli related to cellular stress and pro-oxidant signals, such as reactive oxygen species (ROS), cytokines, inflammatory mediators, and infection. The upregulation of HO-1 or its enzymatic products CO, BV, and BR have been shown to have anti-inflammatory, antioxidant, cell cycle regulation properties in vitro study or animal models of a variety of diseases including asthma [1–3].

Asthma is a chronic inflammatory disease with complex pathogenesis. Different triggers could lead to different types of inflammation. For example, exposure to an allergen in sensitized individuals tends to invoke Th2 high airway inflammation characteristic of increased Th2 cytokine and eosinophil (EOS) infiltration in the airway. On the other hand, respiratory infection or recurrent environmental tobacco smoke exposure tend to induce Th17 or Th1-dominant immune responses and Th2-low airway inflammation characteristic of neutrophil infiltration. A variety of immune cells are involved despite Th2-high or low airway inlfammation. HO-1 expression is significantly upregulated in many immune cells such as dendritic cells (DCs), macrophages [4], mast cells (MCs) [5], basophils (BAs) [6], and T cells [7] in response to cellular stress. Both HO-1 and CO displayed anti-inflammatory, antioxidative stress, and immune regulation properties in an asthma animal model [8,9] and inhibited the proliferation of cultured human airway smooth muscle cells (HASMCs) through downregulation of ERK1/2 activation, which indicated the anti-airway remodeling effects of HO-1. HO-1 has been shown to exert anti-inflammatory effects in both T helper cell type (Th) 2-dominant [6,10,11] and Th17-dominant models of asthmatic airway inflammation [12]. In this article, we will discuss mechanisms by which HO-1 regulates

**Citation:** Xia, Z.; Zhong, W. Immune Regulation of Heme Oxygenase-1 in Allergic Airway Inflammation. *Antioxidants* **2022**, *11*, 465. https:// doi.org/10.3390/antiox11030465

Academic Editors: Stanley Omaye, Elias Lianos and Maria G. Detsika

Received: 6 January 2022 Accepted: 23 February 2022 Published: 26 February 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

immune responses during allergic airway inflammation with a focus on specific immune cells in different stages of inflammation.
