Remodeling and Restraining Lung Tissue Damage Through the Regulation of Respiratory Immune Responses

Tissue Eng Regen Med https://doi.org/10.1007/s13770-022-00516-7 Online ISSN 2212-5469 REVIEW ARTICLE Remodeling and Restraining Lung Tissue Damage Through the Regulation of Respiratory Immune Responses Young Jin Pyung1 • Da-Jeong Park1 • Cheol Gyun Kim1 • Cheol-Heui Yun1,2,3,4 Received: 15 November 2022 / Revised: 13 December 2022 / Accepted: 26 December 2022 Ó Korean Tissue Engineering and Regenerative Medicine Society 2023 Abstract Tissue damage caused by various stimuli under certain conditions, such as biological and environmental cues, can actively induce systemic and/or local immune responses. Therefore, understanding the immunological perspective would be critical to not only regulating homeostasis of organs and tissues but also to restrict and remodel their damage. Lungs serve as one of the key immunological organs, and thus, in the present article, we focus on the innate and adaptive immune systems involved in remodeling and engineering lung tissue. Innate immune cells are known to react immediately to damage. Macrophages, one of the most widely studied types of innate immune cells, are known to be involved in tissue damage and remodeling, while type 2 innate lymphoid cells (ILC2s) have recently been revealed as an important cell type responsible for tissue remodeling. On the other hand, adaptive immune cells are also involved in damage control. In particular, resident memory T cells in the lung prevent prolonged disease that causes tissue damage. In this review, we first outlined the structure of the respiratory system with biological and environmental cues and the innate/adaptive immune responses in the lung. It is our hope that understanding an immunological perspective for tissue remodeling and damage control in the lung will be beneficial for stakeholders in this area. Keywords Adaptive immunity
Innate immunity
Innate lymphoid cell
Macrophages
Protective immune response
Respiratory system
T cell
Tissue damage
Tissue remodeling 1 Introduction Young Jin Pyung and Da-Jeong Park are equally contributed. & Cheol-Heui Yun 1 Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea 2 Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea 3 Institutes of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon-Do 25354, Republic of Korea 4 Interdisciplinary Programs in Agricultural Genomics, Seoul National University, Seoul 08826, Republic of Korea The purpose of tissue engineering is to design functional constructs that restore, maintain, or improve damaged tissues or organs in animals and humans [1]. Lung tissue engineering is an emerging field that focuses on developing replacement devices and tissue regeneration. Lung tissue damage may be caused by viral infections, allergens, physical forces, or other forms of stressors. It is critical to reduce tissue damage since it frequently results in disease or/and sometimes immunological pathology that calls for an understanding of the immunological perspective. Therefore, although numerous factors are needed in tissue engineering [2], immune cell involvement and function should be considered. The majority of immune cell research in the field of tissue engineering focuses on macrophages. It is crucial, however, to remember that it is 123 Tissue Eng Regen Med critical to consider other immune cells, not only macrophages, in tissue engineering. The lung is an important immunological interface. The respiratory tract is exposed to incoming air that contains both harmless ambient components and potentially harmful substances, including allergens and pathogenic airborne microorganisms. Stimuli such as microbe-related substances or tissue damage could actively induce systemic and/or local immune responses. Therefore, to protect the host in such a close contact zone, the respiratory immune system must be fine-tuned and quick to react, with the ability to immediately detect harmful microbes [3, 4]. Defenses in the lung are carried out primarily by immune cells, including alveolar macrophages that are present in the airways and neutrophils that migrate upon receiving alarming signals, such as chemokines [5]. Immune cells respond to foreign substances by releasing various effector molecules, such as chemokines, cytokines, defensins, or mucins [6]. Needless to say, understanding the mechanisms for the protective immune responses that take place within the lung is crucial for tissue engineering. Early recognition of pathogens with an immediate response by the innate immune system and prompt removal of these pathogens by means of defensive mechanisms demonstrate the effectiveness of innate immune cells in the airway and lung. When innate immune cells such as macrophages and dendritic cells (DCs) recognize pathogens via pathogen recognition receptors (PRRs), they are activated and subsequently produce proinflammatory cytokines. Moreover, innate lymphoid cells (ILCs) are present in various mucosal tissues, including the lung, which serve as early responders to invading pathogens and allergens [7]. Notably, type 2 ILCs are the most prevalent ILCs in the lung [8], as they play important roles in lung tissue homeostasis and remodeling [9]. Innate immunity provides an effective initial defense against infections, although many pathogenic microbes have evolved resistance. In turn, we as hosts have developed adaptive immune responses. It has been proposed that the increased number of localized infections and injuries brought on by the unique jaw structures and predatory lifestyle of primitive jawed fish (placoderms) led to the evolution of the adaptive immune system of vertebrates [10]. Adaptive immune systems display a high degree of specificity together with remarkable memory cell and antibody secretion properties. There are two types of lymphocytes, T cells and B cells, that mediate adaptive immune responses. T cells can be further divided into CD4? and CD8? T cells [11]. In addition to assisting in the activation of CD8? T cells, CD4? T cells facilitate the differentiation and maturation of B cells to secrete antibodies and activate macrophages to clear ingested microbes. Effector CD8? T cells, also called 123 cytotoxic T lymphocytes, can kill infected target cells directly but only after antigen processing and presentation by DCs [12]. It has been suggested that CD4? and CD8? T cells play critical roles not only in protection but also in damage control in lung tissue. As a result, maintaining lung tissue requires remodeling and damage control of these tissues via both innate and adaptive immunity, respectively. In this review, we first provide an overview of the respiratory tract along with various factors that affect tissue damage. We then focus on immune cell traits for lung tissue engineering, specifically ILCs as a component of inna (...truncated)