Mini Review: The Role of Myeloid Immune Cells in Lung Epithelial Repair

Graphical Abstract

Introduction

The lungs, like the skin, are organs with one of the greatest burdens of exposure to external insults including smoking, pollution, and pathogens, all of which can result in lung injury (1, 2). Injury directly impacts both the bronchial epithelium and the alveolar epithelium, made up of thin type 1 alveolar epithelial (AT1) cells and surfactant-producing type 2 alveolar epithelial (AT2) cells. After injury, lung tissue has some capacity to repair, though this ability declines with aging (3). In non-pathological repair, AT2 cells, the stem cells for the epithelial layer, can differentiate into new AT1 cells (4). This type of homeostatic repair is perfectly timed, proportionate, and returns the epithelium to its normal architecture. In contrast, pathologic remodeling perpetuates detrimental, disproportionate signals which prevent the tissue from returning to homeostasis, potentially leading to chronic pulmonary diseases such as fibrosis (5).

Understanding the process of healthy, non-pathological lung repair after injury is vital to maintaining proper structure and function of the lungs and requires an orchestra of many cell types, including basal, ciliated, and secretory cells such as goblet cells, with different proportions associated with different regions of the respiratory tract (6). An underappreciated participant in the process is the immune system, and studies show that immune cells may have a bigger impact than previously thought (7–10). Myeloid immune cells are of particular interest because they are among the first responders to alveolar injury and remain involved over the full arc of the response to injury (11). In this mini-review, we summarize recent research on the impact of mononuclear phagocytes - monocytes, macrophages, and dendritic cells (DCs) - and granulocytes - neutrophils, eosinophils, basophils and mast cells - to lung epithelial repair in otherwise healthy contexts. While other cells such as lymphocytes, endothelial cells, and fibroblasts play an important role in lung repair, this mini-review will focus on the contribution of immune cells from the myeloid compartment.

Mononuclear Phagocytes

This leukocyte group consists of monocytes, macrophages, and DCs. Because monocytes can differentiate into both macrophages and DCs, this section focuses on the roles of macrophages and DCs in healthy lung repair. Beyond their established functions in pathogen and debris clearance and antigen presentation to T and B cells, these cells serve as key regulators of lung tissue repair (12).

Macrophages

Macrophages in the lung can be tissue resident or recruited originally as monocytes from the circulation or bone marrow after an injury such as infection. Tissue resident macrophages include alveolar macrophages, which reside in the airspace and are the first line of surveillance and defense, and interstitial macrophages, which reside in the lung parenchyma where they regulate immune responses and tissue homeostasis (13). Importantly, even these well-defined groups of macrophages contain diverse and dynamic subpopulations, a complexity increasingly revealed with the widespread use of single-cell sequencing (14). Initially guided to damaged sites by cytokine signals, macrophages are classically associated with phagocytosis of pathogens and particulates. However, beyond host defense, data show macrophages potentially play essential roles in healthy lung repair through interactions with multiple cell types, including direct and indirect effects on epithelial cells.

Both clinical and translational studies have shown macrophage populations are vital for healthy epithelial repair. Macrophages polarized with bronchoalveolar lavage fluid from human patients with moderate to severe acute respiratory distress syndrome (ARDS) promoted migration and proliferation of alveolar epithelial cells, through the hepatocyte growth factor (HGF) pathway (15). In healthy lung repair, HGF is recognized by the Met receptor on epithelial cells which induces proliferation and inhibits fibrotic remodeling (16). Not only do monocyte-derived macrophages (recruited macrophages) accumulate after pneumonectomy utilizing the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 (CCL2CCR2) axis, genetic loss of function of CCR2 impairs lung growth, which is restored with adoptive transfer of wild-type bone marrow (Figure 1A) (8). In a model of viral pneumonia and bleomycin, Notch2 blockade, an important signal in monocyte differentiation, prior to injury resulted in the generation of a unique group of interstitial macrophages which decreased weight loss, lung fibrosis, and inflammation (17). Interestingly, a specific type of short-lived monocyte derived macrophage with a unique lymphocyte antigen 6 complex, locus G⁺ (Ly6G⁺) signature historically associated with neutrophils cluster in a different injury model of influenza. These Ly6G⁺ macrophages are recruited to “perilesional areas”, or areas around damaged tissue, where they cluster with AT2s. Not only are they able to act in their role of phagocytosis in this instance, but their deletion also impairs epithelial repair. Translationally, this study showed the presence of similar macrophages in humans with suspected pneumonia (Figure 1B) (9).

Figure 1. Macrophage interactions with the lung epithelium in healthy repair.

(A) Following pneumonectomy, CCR2⁺ monocytes are recruited from the bone marrow via the CCL2 signaling and differentiate into macrophages. Loss of CCR2 impairs epithelial repair after pneumonectomy. (B) Ly6G+ monocyte-derived macrophages, bearing a surface marker historically associated with neutrophils, are recruited to perilesional areas where they cluster with AT2 cells and promote epithelial repair after influenza injury. (C) Alveolar macrophage-derived oncostatin M counteracts type I interferon-mediated suppression of epithelial proliferation, maintaining AT2 transcriptional states and promoting barrier repair after viral pneumonia. (D) Macrophage-secreted TFF promotes epithelial proliferation via upregulation of Wnt4 and Wnt16 following hookworm-induced lung injury. Recombinant Wnt4 and Wnt16 restore the proliferative defect in TFF-deficient animals. (E) Following bleomycin injury, interstitial macrophage-derived IL-1β drives AT2 cells into a transitional progenitor state bridging AT2-to-AT1 differentiation, a process requiring HIF-1α-mediated glycolytic reprogramming. (F) Alveolar macrophages constitutively secrete SOCS1 and SOCS3 proteins via extracellular vesicles, which are taken up by alveolar epithelial cells and dampen JAK-STAT-mediated inflammatory signaling. (G) Macrophage-derived exosomes carry BMPR2, which interacts with epithelial BMPR1B to drive AT2-to-AT1 differentiation after blast-induced lung injury. Created in BioRender. Kumar, A. (2026) https://BioRender.com/jia7qf0.

Macrophages may also release factors that allow for repair in various injury scenarios, including via oncostatin M, trefoil factor family (TFF), interleukin (IL)-1β, and tumor necrosis factor alpha (TNF-α). In response to viral pneumonia, type I interferons suppress epithelial proliferation and induce epithelial cell death. However, this suppression must be stopped in order to allow for epithelial repair. Interestingly, a study showed that the release of alveolar macrophage-derived oncostatin M (a cytokine in the interleukin 6 family) counteracts type I interferon–mediated immunopathology, maintains AT2 transcriptional states at baseline and promotes AT2 proliferation and epithelial barrier repair. Mice lacking oncostatin M exhibit heightened type I interferon responses and increased mortality after infection (Figure 1C) (18). Moreover, after hookworm induced lung injury, macrophage specific deletion of TFF (a secreted peptide that promotes mucosal repair) reduced AT2 cell proliferation. Mechanistically, macrophages with TFF upregulate Wnt4 and Wnt16 in response to epithelial damage. Recombinant Wnt4 and Wnt16 in TFF deficient animals restored the proliferative defect, highlighting the TFF/Wnt axis in macrophage to epithelial cell repair (Figure 1D) (19). Furthermore, in a bleomycin induced lung injury model, IL-1β produced by interstitial macrophages drives AT2 cells into a transitional state that bridges AT2 to AT1 differentiation. This differentiation then occurs via hypoxia-inducible factor 1 alpha (HIF-1α) mediated glycolytic signaling (Figure 1E) (20). In a lipopolysaccharide model, resident alveolar macrophages release TNF-α, which stimulates alveolar epithelial cells to upregulate granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in epithelial proliferation. Importantly, this signal disappeared with GM-CSF deficient mice, establishing the TNF-α/GM-CSF axis (21). Macrophage epithelial signaling can also be bidirectional. In naphthalene-induced bronchial injury, IL-33 released from damaged bronchial epithelial cells activates suppression of tumorigenicity 2 (ST2⁺) macrophages and promotes club cell repair (22).

Macrophages also communicate with epithelial cells through extracellular vesicles (EVs), nanosized membrane-bound particles carrying bioactive cargo including proteins and non-coding ribonucleic acids (RNAs) (23). Even in the absence of injury, alveolar macrophages constitutively secrete suppressor of cytokine signaling 1 (SOCS1) and suppressor of cytokine signaling 3 (SOCS3) proteins in vesicles taken up by alveolar epithelial cells, dampening Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway mediated inflammation (Figure 1F). This secretion decreases upon lipopolysaccharide (LPS) stimulation, suggesting a homeostatic brake released in the setting of injury (24). The same group of investigators observed this effect in allergic airway inflammation (25). More directly relevant to repair, proteomic profiling of macrophage derived exosomes identified bone morphogenetic protein receptor type 2 (BMPR2) as a component that interacts with epithelial bone morphogenetic protein receptor type 1B (BMPR1B) to drive AT2-to-AT1 differentiation after blast-induced lung injury (Figure 1G) (26). While macrophage to epithelial cell communication via EV is a relatively new area of research, these findings establish EVs as functionally relevant to healthy epithelial repair in the lung.

Collectively, these mediators do not define a single reparative macrophage subset but instead reflect context-dependent outputs of distinct, potentially overlapping states. HGF was associated with anti-inflammatory CD163^high, IL-10–producing human alveolar macrophages, although its reparative activity was demonstrated ex vivo and in vitro (15). Oncostatin M is produced by tissue-resident alveolar macrophages at baseline and by recruited monocytes and monocyte-derived macrophages after viral injury, with support from organoid and in vivo genetic studies (18). TFF/Wnt axis signaling was attributed more broadly to CD11c⁺ lung myeloid cells, including alveolar macrophages, and has not been assigned to a discrete subset (19). Conversely, IL-1β was localized primarily to interstitial macrophages, although its direct effects on AT2 state transitions were established mainly in organoids (20). In the TNF-α/GM-CSF axis, resident alveolar macrophages provide TNF-α, whereas GM-CSF is produced by epithelial cells, as supported by coculture and in vivo mouse studies (21). Because these studies generally did not assess mediator co-expression in individual macrophages, the degree of overlap remains uncertain. The dominant pathway likely depends on macrophage origin and location, the injury and epithelial target, and the timing of the response; moreover, transient inflammatory signaling may support repair, whereas its persistence can promote maladaptive remodeling. Thus, macrophage-mediated epithelial repair is best viewed as a spatially and temporally regulated continuum of activation states, with several pathways still requiring direct in vivo and human validation.

Dendritic cells

There is a paucity of literature on the contribution of dendritic cells (DCs), which is largely inferred from their immunological functions. DCs are difficult to study given shared surface markers and the lack of widespread use of depletion strategies. However, evidence from non-pulmonary systems suggests broader roles for DCs than previously appreciated (27). Most available data derive from pulmonary fibrosis models and remain contradictory, potentially due to differences in DCs studied (28–30). The role of DCs in healthy repair is a clear opportunity for future research.

Granulocytes

Granulocytes include neutrophils, eosinophils, mast cells, and basophils. They have an existing, well characterized role in allergic disease and host defense. On one hand, neutrophils are usually characterized to promote type 1 inflammation (relevant against bacterial and fungal infections and in neutrophilic asthma). On the other hand, eosinophils, mast cells and basophils are associated with type 2 inflammatory responses (relevant in type 2-driven asthma and helminth infections). Although type 2 inflammatory responses are usually associated with lung tissue repair and type 1 inflammation with lung injury, most evidence from granulocytes points to neutrophils as the most relevant granulocyte in lung epithelium repair. This area of emerging research reveals that granulocytes may have more of a role than previously thought including direct cell-to-cell interaction with alveolar epithelial cells and modulation of other leukocytes indirectly promoting lung epithelial repair. Here we discuss the specific contribution of granulocytes to healthy lung epithelium repair.

Neutrophils

Although the most abundant circulating leukocyte, neutrophils are not primary residents of healthy lung tissue; instead they form a marginated pool within the pulmonary vasculature, enabling rapid deployment to the alveolar space as one of the first responders to injury (Figure 2A) (31, 32). Upon recruitment, neutrophils, besides contributing to immune cell recruitment and clearance of debris, can also induce collateral immunopathology through inflammatory pathways (33, 34). More recent studies involving advanced techniques such as genetic fate mapping and single-cell sequencing have uncovered key roles of these cells in tissue repair and maintenance of tissue homeostasis associated with their previously underestimated heterogeneity and plasticity (35).

Figure 2. Granulocytes at play in healthy lung epithelial repair.

(A) Granulocytes including neutrophils, eosinophils, basophils and mast cells are recruited from pulmonary vasculature. (B) Polarization of anti-inflammatory neutrophils (N2) promote epithelial remodeling and repair through secretion of matrix metalloproteinase-9, cytokines and extracellular vesicles (containing microRNA-223), which can also promote the polarization towards pro-resolving macrophages, which in turn secrete cytokines and lipid mediators that promote epithelial repair. (C) Efferocytosis of neutrophils by macrophages also promote the polarization of pro-resolving macrophages. (D) Neutrophils can promote epithelial proliferation and repair by activating β-catenin signaling in alveolar type 2 (AT2) cells. (E) Release of low levels of defensins promote airway epithelial repair by enhancing proliferation and migration. (F) Eosinophil peroxidase (from granules) and TGF-β promote epithelial proliferation, migration and epithelial-mesenchymal transition; and amphiregulin inhibits apoptosis in AT2 cells and also stimulates the proliferation and differentiation of AT2 cells. (G) Mast cell-derived tryptase promotes gap closure (in vitro experiments), migration and cellular speed, as well as increase expression of the proliferation marker Ki-67. (H) Basophils produce IL-4 that promotes apoptosis in neutrophils and efferocytosis from macrophages, promoting lung epithelial repair. Created in BioRender. Kumar, A. (2026) https://BioRender.com/tnm80om.

Established evidence associating neutrophils to alveolar epithelial repair originates from neutropenic models showing impairment of AT2 proliferation, delayed repair, and enhanced inflammation (36, 37). The beneficial role of neutrophils in tissue repair is associated with their reported roles as anti-inflammatory, pro-angiogenic and regenerative cell function. Related to this, functional heterogeneity of neutrophils has been defined based on three parameters: spatial (response and adaptation to local signals), temporal (maturation state and ageing) and disease context (type of disease and/or existing conditions). Overall, the outcome of the neutrophil response to injury is context-dependent, accounting for the initial insult, local microenvironment, and neutrophil heterogeneity (38).

Two functionally different subtypes of neutrophils have been described, N1 (pro-inflammatory and anti-tumor) and N2 (anti-inflammatory and pro-tumor), originally identified in tumor pathology. Differentiation towards the N2 subtype requires transforming growth factor beta (TGF-β) and granulocyte colony-stimulating factor (G-CSF) and N2 neutrophils increase during tissue repair with inflammation resolution (Figure 2B) (39). The importance of this shift is supported by ARDS-like injury models, where neutropenia or G-CSF deficiency impaired epithelial repair and increased alveolar permeability (37). Neutrophil aging adds another layer of regulation, as neutrophils ‘disarm’ by losing granule content during their lifetime in circulation. Disarmed neutrophils have reduced neutrophil extracellular trap (NET) formation capacity, protecting lungs from potential neutrophil-mediated injury in a mechanism dependent on the chemokine receptor C-X-C motif chemokine receptor 2 (CXCR2) and the circadian clock (40).

In terms of interaction with other myeloid cells, N2 neutrophils enhance repair by secreting factors that reprogram macrophages (41). A key mechanism is macrophage-mediated efferocytosis, where apoptotic neutrophils are actively engulfed, enabling the silent removal of inflammatory cells in contrast to lytic death pathways which amplify inflammation via release of inflammatory contents (42). Efferocytosis reprograms macrophages toward a pro-resolving phenotype (anti-inflammatory), inducing anti-inflammatory cytokines (e.g., TGF-β, IL-10) and specialized lipid mediators (e.g., resolvins D1, D2, E4, lipoxin A4 and maresin) while suppressing pro-inflammatory signals (Figure 2C) (34, 41, 43–45). In the lung, this effect on macrophages involves the inhibition of mitochondrial reactive oxygen species (ROS) by the neutrophil myeloperoxidase (MPO), supporting the resolution of lung inflammation and enabling epithelial repair (46–48). Related to this, neutrophil-derived extracellular vesicles have also been shown to reprogram macrophages toward pro-resolving state by suppressing pro-inflammatory cytokines while enhancing IL-10 and pro-resolving lipid mediators, and boost efferocytosis (49–51). Phosphatidylserine on these vesicles enhances efferocytosis of neutrophils (52). Another potential mechanism through neutrophil-derived vesicles is the intercellular transfer of microRNA-223 to epithelial cells. This transfer suppresses poly(ADP-ribose) polymerase 1 (PARP-1) expression, reducing inflammation and tissue damage. Loss of miR-223 exacerbates injury, while its overexpression is protective, highlighting a mechanism by which neutrophils directly modulate epithelial responses during lung repair (53).

During transmigration across the lung epithelium, neutrophils can promote epithelial repair by activating β-catenin signaling in AT2 cells, largely through neutrophil elastase-mediated cleavage of E-cadherin. This pathway drives AT2 proliferation and supports restoration of epithelial integrity. β-catenin signaling also limits barrier disruption during neutrophil passage, while its inhibition delays repair (Figure 2D) (54). Given the role of AT2 cells, neutrophil-induced β-catenin activation represents a key mechanism linking inflammation to epithelial repair (37, 55, 56). Interestingly, it has been speculated that neutrophil transepithelial migration occurring without major barrier disruption, can also promote epithelial repair by the release of neutrophil adenosine triphosphate (ATP)-derived adenosine, which restores tight junctions, although excessive migration during inflammation can still cause epithelial damage (57).

In addition, roles of neutrophil-derived metalloproteinases and defensins have been associated with lung tissue repair (36). Importantly, neutrophils are the only cells capable of releasing matrix metalloproteinase-9 (MMP-9) free of its endogenous inhibitor, delivering highly active MMP-9 to angiogenic sites (58). In ventilator-induced lung injury, neutrophil depletion increased inflammation and delayed epithelial repair. This effect was largely attributed to neutrophil-derived matrix metalloproteinase-9 (MMP-9), which facilitates extracellular matrix remodeling and epithelial restitution. Consistently, exogenous MMP-9 restored repair in neutropenic models and improved wound healing in human samples, underscoring its critical role in lung epithelial repair (36). In terms of defensins, neutrophil-derived human neutrophil peptides 1–3 (HNP1–3) can directly promote airway epithelial repair by enhancing proliferation, migration, and mucin production. At physiological concentrations, they stimulate epithelial cell growth, while higher levels are cytotoxic. Mechanistically, defensin-driven proliferation involves mitogen-activated protein (MAP) kinase signaling and, in some contexts, epidermal growth factor receptor pathways (Figure 2E) (59, 60).

Collectively, neutrophils are not merely early inflammatory responders but highly adaptable regulators of lung epithelial repair, with their effects dictated by subset heterogeneity, activation state, and microenvironmental cues. Through coordinated mechanisms (e.g. macrophage reprogramming, efferocytosis, epithelial signaling, and matrix remodeling), they actively promote resolution, repair, and barrier restoration. Balancing their reparative versus injurious functions remains central to effective lung healing.

Eosinophils

Eosinophils are classically associated with responses to allergens and parasitic infections, but they have also been shown to have a developmental peak during lung septation and alveolarization (61). Moreover, despite the known injurious effects of eosinophils on the lung epithelium during inflammation, eosinophils have been found to be necessary for resolution of inflammation and tissue repair particularly in asthma models (62). This depends on the state of the eosinophils, and bidirectional signaling between eosinophils and airway epithelial cells (6). Different eosinophil subsets may co-exist and perform different functions. Type 1 eosinophils may preferentially interact with fibroblasts and assist in building extracellular matrix (ECM) scaffolds, whereas Type 2 eosinophils may directly interact with the epithelium and participate in scaffold removal and resolution of repair (63).

Eosinophil granules store numerous cytokines, enzymes, and growth factors. Eosinophil peroxidase (EPX), the most abundant secondary granule protein, can promote proliferation, migration and epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (BEAS-2B) via Phosphoinositide 3-kinase (PI3K) signaling (64). Eosinophils can also release TGF-β and amphiregulin, two major cytokines involved in lung repair (Figure 2F). TGF-β regulates epithelial proliferation essential for airway basal stem cell-mediated lung repair (65) and is the most powerful inducer of EMT, a process that facilitates epithelial migration (66). Consistent with this, human eosinophils can promote EMT in human bronchial epithelial cells (BEAS-2B) (67) in a TGFB1 dependent manner (68). Amphiregulin facilitates tissue repair by mediating epidermal growth factor receptor (EGFR)-induced inhibition of apoptosis and stimulation of AT2 cell proliferation and differentiation (63, 69, 70). Airway epithelial cells can in turn express increased amounts of Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) during allergic inflammation, which can promote the survival of tissue eosinophils (71). While this bidirectional crosstalk can support epithelial survival and proliferation, eosinophils remain capable of significant epithelial injury and more studies are necessary to fully understand the heterogeneity and plasticity of eosinophils during inflammation and repair.

Mast Cells

Mast cells are key components of the lung innate immune system and mediate allergic reactions (e.g. asthma) through the release of secretory granules. Unlike most leukocytes, mast cells have the ability to release the content of these granules within seconds to minutes of activation (72). Mast cells go through different phases early upon activation, including the inflammatory and proliferative phases, where mast cells release pro-inflammatory substances and proliferate significantly. In the remodeling phase, mast cells decrease in number, and their functional activity (such as degranulation) sharply decreases (73).

Upon activation, mast cells release three classes of mediators 1) pre-formed mediators (e.g. histamine and proteases such as chymase and tryptase), 2) secondary lipid mediators (e.g. prostaglandins and cysteinyl leukotrienes) and 3) cytokines, chemokines and growth factors (e.g. TNF-α, IL-6, vascular endothelial growth factor (VEGF)) (74). The presence and abundance of mediators chymase and tryptase serves as a categorization of mast cells phenotype; mast cells containing both are associated with disease whereas mast cells containing primarily tryptase are associated with healthy airways (75).

In vitro data show that tryptase promotes epithelial repair via gap closure, migration, and increased expression of proliferation marker Ki-67 (76, 77), in part regulated by protease-activated receptor-2 (PAR2) signaling (Figure 2G) (77). In contrast, chymase suppresses fibronectin expression and reduces airway epithelial cell migration (78). Importantly, in pathological scenarios such as asthma, current data suggest that mast cells are largely related to detrimental epithelial remodeling (77, 79). The ultimate impact of mast cells on healthy epithelial repair may be related to this tryptase/chymase balance, though our understanding of how and when mast cells regulate lung epithelial repair is still limited.

Basophils

Basophils are low in abundance and there are very few studies addressing their potential role in lung repair. Importantly, basophils are key mediators of allergic responses through a high production of IL-4 and IL-13. A study demonstrated that basophil depletion impaired resolution of LPS-induced ARDS in an IL-4–dependent manner, where IL-4 produced by basophils acted on neutrophils to suppress the anti-apoptotic gene and pro-inflammatory mediator expression (80). These data suggest that basophil-derived IL-4 can promote apoptosis in neutrophils and efferocytosis by macrophages, promoting lung epithelial repair (Figure 2H). In this context, basophils have been shown to regulate alveolar macrophage function (81) and also modulate innate lymphoid cell-2 activity (82), suggesting the potential downstream effects on modulating the effect of other leukocytes to promote lung re-epithelization, which still remain to be fully defined.

Interactions between myeloid cells during repair

Across several experimental models, resolution and repair are associated with attenuation of neutrophil-dominant inflammatory programs and the emergence of pro-resolving or type 2-associated responses involving reparative macrophages, eosinophils, basophils, and other immune cells (8, 62, 80). Type 2-associated cytokines and myeloid-derived growth factors can promote reparative macrophage programs, epithelial proliferation, differentiation, and restoration of barrier integrity (8, 18, 83). However, studies directly tracking coordinated interactions among multiple myeloid-cell populations throughout the transition from inflammation to repair remain limited. Available evidence nevertheless demonstrates functional communication between neutrophils and macrophages through secreted mediators and efferocytosis, as well as communication between basophils, macrophages, and neutrophils during lung homeostasis and injury resolution (41, 46, 80, 81). These interactions are mediated by cytokines, chemokines, growth factors, extracellular vesicles, and mechanisms regulating local cell abundance and clearance, including apoptosis and efferocytosis (18, 41, 46, 80, 81). Defining these dynamic intercellular networks will be essential for understanding how immune responses support effective epithelial regeneration or, when dysregulated or prolonged, contribute to pathological lung remodeling.

Conclusions

Myeloid cells represent the majority of immune cells in the pulmonary vasculature, as well as in the airways and lung parenchyma. As shown here, these cells are crucial for lung epithelium repair. Particularly, Myeloid cells regulate epithelial proliferation, migration, differentiation, and survival through both direct cellular interactions and indirect mechanisms involving cytokines, growth factors, extracellular vesicles, and matrix remodeling. Myeloid immune cells’ pivotal role in the process of non-pathological lung repair is highlighted by cell depletion and specific loss of function approaches. However, these same populations drive aberrant repair when their activity is dysregulated or prolonged. Therefore, understanding and distinguishing reparative myeloid responses from pathological ones – particularly in terms of magnitude and timing of response – is a vital avenue of future research. Importantly, learning more about the impact of myeloid cells on repair could open the door to potentially life changing treatments that restore normal epithelial architecture after injury.