---
title: "Macrophage polarization and mesenchymal stromal/stem cell therapy in acne: article availability an"
id: "frontiers-in-immunology-18-targeting-macrophage-polarization-mechanisms-and-potential-of-mesenchymal"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-18-targeting-macrophage-polarization-mechanisms-and-potential-of-mesenchymal"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1889795"
published_at: "2026-08-12T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Macrophage polarization and mesenchymal stromal/stem cell therapy in acne: article availability an
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1889795)
- **Published At:** 2026-08-12T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The provided source content contained only Frontiers in Immunology website navigation and metadata; the substantive article text for the narrative review was not included in the source. - Title of the missing article indicates it reviews **macrophage polarization** and the potential of **mesenchymal stromal/stem cells (MSCs)** for **acne** treatment, but the source did not supply the review's data, mechanisms, or conclusions. - Key specifics such as study summaries, mechanistic pathways, preclinical or clinical evidence, therapeutic protocols, safety data, and recommendations were not reported in the supplied content. - Because only site navigation and journal information were available, no direct clinical or experimental facts from the narrative review can be extracted or rewritten without risking fabrication. - The document below (rewrittenContent) therefore (1) confirms the absence of the article body in the supplied source, (2) outlines the expected structure and likely topics that such a narrative review would address based on its title, and (3) provides guidance on how to access the full article for clinical use. All specific findings, data points, and recommendations were not reported in the source and are not claimed here.
## Clinical Analysis & Structured Key Points
Frontiers | Targeting macrophage polarization: mechanisms and potential of mesenchymal stromal/stem cells therapy in acne treatment— a narrative review REVIEW article Front. Immunol. , 12 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1889795 Published in Frontiers in Immunology Inflammation 7 impact factor 11.3 citescore Part of a Research Topic Immunology of Skin Health and Disease Submission open 35k views 21 articles Editor & Reviewers Edited by E S Emanuele Scala Reviewed by H K HARUNA KIMURA M L Mengguo Liu S C Stefana Cretu Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Figure 5 View in article Table 1 This table shows the standard clinical treatments for acne, including treatment examples, importance, mechanism of action, common side effects, solutions for side effects. View in article REVIEW article Front. Immunol. , 12 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1889795 Targeting macrophage polarization: mechanisms and potential of mesenchymal stromal/stem cells therapy in acne treatment— a narrative review Y Y Yibing Yang 1 N L Nianlv Luo 1 L L Linyan Li 2,3 Y Z Yufen Zhao 4 X X Xiaoliang Xu 2,3 H W Hanxiao Wei 2,3 Y Y Ying Yang 1 W Y Wen Yan 1 T Z Tao Zhang 1,2,3 * 1. Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, China 2. Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, China 3. Guizhou Biomanufacturing Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, China 4. Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China See more Article metrics View details Abstract Acne vulgaris(AV) is a clinically common skin disease. Globally, about one in ten individuals is affected by it. Current research on acne primarily focuses on the following four areas: first, the inflammatory response; second, sebum metabolism disorders; third, the colonization of Cutibacterium acnes (C. acnes); and fourth, abnormal keratinization of the pilosebaceous duct. Although the exact pathogenesis of this condition has not yet been fully elucidated, the dual polarization of macrophages play a crucial role in the onset, progression and outcome of acne. As key effector cells in the human immune system, macrophages can exhibit different phenotypes in the microenvironments of various diseases: the classical activated phenotype (M1), the alternative activated phenotype (M2), and a subset characterized by the expression of trigger receptor 2 (TREM2) in myeloid cells. Currently endorsed international acne therapy, encompassing topical agents, systemic drugs, and physical therapies, demonstrates efficacy but frequently elicits a range of adverse effects. Therefore, there is a pressing need for a new, ideal treatment approach. Extensive research on stem cells and their derivatives in recent years has shown that mesenchymal stromal/stem cells (MSCs) possess significant immunomodulatory and anti-inflammatory capabilities, particularly in terms of influencing macrophage polarization. They promote the transition of macrophages to the anti-inflammatory M2 phenotype, which may play a role in the recovery process of acne. The unique advantage of MSCs therapy is that it is not simply antibacterial or anti-inflammatory as traditional therapies; rather, it may alleviate inflammation and promote skin tissue repair by promoting polarization of M2 macrophages. At the same time, it is expected to avoid the common adverse reactions in current acne treatment methods. This paper aims to provide a narrative review on the function of macrophages in skin tissue, the core role of inflammatory responses in acne pathogenesis, the multifaceted functions of macrophages in acne, the mechanisms through which MSCs regulate macrophage polarization, the current guideline-recommended standard treatment protocols for acne, and the feasibility of MSCs and their derivative transplants as a therapeutic strategy for alleviating acne inflammation. 1 Introduction Acne vulgaris is a common chronic inflammatory dermatological condition that affects the hair follicle-sebaceous gland unit, influencing roughly one in ten individuals globally and ranking as the eighth most widespread disease worldwide ( 1 , 2 ). Globally, the age-standardized prevalence of acne among adolescents and young adults aged 10-24 years increased from 8563.4 cases per 100,000 people in 1990 to 9790.5 cases per 100,000 people in 2021, with an annual increase of 0.43. The burden of acne among adolescents and adults continues to increase in almost all countries ( 3 ). Acne predominantly impacts the cheeks and forehead, subsequently affecting the chest and back, frequently resulting in a symmetrical distribution. It is often associated with enlarged pores and excessive sebum secretion. Clinical symptoms include several acne-like lesions, including comedones, papules, pustules, nodules, cysts, and scars ( 4 ). Although inflammatory erythema and persistent scarring resulting from severe acne are not uncommon in clinical practice, they can profoundly affect the physical and psychological well-being of adolescents. This may result in psychological problems, including reduced self-identity, social anxiety, and depressive mood, thereby heightening the risk of emotional and mental diseases. In severe instances, it may even contribute to suicidal inclinations ( 5 , 6 ). Consequently, acne has emerged as a pressing social concern that necessitates a resolution. Current guidelines advocate for acne treatments encompassing topical drugs (such as retinoids, benzoyl peroxide (BPO), azelaic acid, antibiotic ointments), oral medications (such as antibiotics, isotretinoin, corticosteroids, and antiandrogens), and physical therapies. Although current acne treatment protocols are effective, they often provoke adverse reactions, including skin irritation, dryness, and disruption of the skin microbiota by topical medications, along with teratogenic consequences. Concerns have been raised about the rise of antibiotic-resistant microorganisms ( 7 – 10 ). Therefore, novel, ideal therapeutics that address the fundamental pathophysiology of acne while minimizing local and systemic adverse effects are urgently needed. As acne treatment grows more challenging, investigating new targets and mechanisms has become a pressing issue in current acne research. The pathogenesis of acne is not fully understood, although it is mostly linked to factors such as genetics, androgen-induced overproduction of sebum, keratinization of the sebaceous duct, proliferation of C. acnes, and immune-inflammatory reactions. The immunoinflammatory response remains continuous throughout the full course of acne formation ( 11 ). Macrophages are essential to the inflammatory response and serve as pivotal constituents of the immune system, significantly contributing to the maintenance of skin homeostasis. Given the central role of inflammation in the pathogenesis of acne vulgaris, macrophages also play a significant role in the development, progression, and outcome of this condition ( 12 , 13 ). Macrophages demonstrate anti-acne properties through the regulation of lipid metabolism, secretion of anti-inflammatory substances, and phagocytosis; nevertheless, their excessive activation may facilitate inflammatory responses and scar formation, hence exacerbating disease progression ( 14 ). In recent years, the concept of “smoldering inflammation” has garnered increasing attention. Smoldering inflammation manifests as a low-intensity but persistent pathological state that is typically lacking the clinical manifestations of acute inflammation. However, at the tissue and cellular levels, it leads to persistent inflammatory infiltration. Research on this inflammation has primarily focused on multiple sclerosis ( 15 – 18 ), cardiovascular disease ( 19 , 20 ), metabolic disorders, autoimmune diseases, cancer, and allergic diseases, serving as a key driver of the progressive deterioration of these conditions ( 21 ). Acne is essentially a chronic inflammatory skin disease characterized by chronicity, persistence, and recurrent flare-ups. This aligns closely with the concept of “smoldering inflammation.” This persistent, low-intensity inflammatory response that is difficult to resolve may be a key factor in the recurrence and chronicity of acne. In recent years, stem cell-based therapies have achieved promising outcomes in the treatment of various conditions, including graft versus host disease ( 22 ), autoimmune disorders ( 23 , 24 ), osteonecrosis of the femoral head ( 25 ), spinal cord injury ( 26 ), Parkinson’s disease ( 27 ), and skin wound healing ( 28 ). MSCs, due to their multipotent differentiation capacity, immunomodulatory characteristics, and tissue repair capacities, have significant potential for the treatment of inflammatory and autoimmune skin disorders, such as psoriasis, atopic dermatitis, contact dermatitis, alopecia areata, systemic sclerosis, and systemic lupus erythematosus, and others ( 29 – 35 ). Particularly, their capacity to modulate macrophages may offer a novel therapeutic approach for acne in the future. Therefore, investigating the role of macrophages in the onset, progression, and outcome of acne and exploring the potential of MSCs and their derivatives to treat acne by regulating macrophage polarization holds both theoretical and practical significance. This narrative review first introduces the functions of macrophages in the skin tissue, with a focus on the pivotal role of the inflammatory reactions in the etiology of acne. Subsequently, we reactions the intricate relationships between lipid metabolism, the colonization of C. acnes, the inflammatory response, scar formation, and macrophages. Additionally, we systematically summarize the mechanisms by which MSCs regulate the polarization of macrophages. Finally, we systematically review the current guideline-recommended acne therapy regimens, innovative treatment strategies based on macrophage polarization, and investigate the feasibility of MSCs and their derivatives transplantation as innovative therapeutic approaches, aiming to provide new insights into the pathogenesis and treatment of acne. 2 The function of macrophages in cutaneous tissue 2.1 Classification, origin, and function of cutaneous macrophages The macrophages in the dermis are categorized into two types: tissue-resident and infiltrating. Tissue-resident macrophages predominantly derive from the yolk sac and fetal liver during embryogenesis and sustain their population postnatally via local proliferation. They are extensively distributed across the epidermis, dermis, and surrounding hair follicles, with notably high concentrations near blood vessels and nerves in the dermis ( 36 ). Infiltrating macrophages originate from monocytes, which are derived from hematopoietic stem cells in the bone marrow, and migrate to the skin solely under inflammatory or injurious conditions. They predominantly aggregate at locations of inflammation or injury, including acne lesions, eczema, or wounds ( 37 , 38 ). The tissue-resident macrophages in the epidermis are predominantly Langerhans cells (LCs), which originate from yolk sac progenitor cells and fetal liver monocytes. These cells migrate to the epidermis during embryonic development and sustain their number through self-renewal under homeostatic conditions. Circulating monocytes move to the epidermis to replace LCs populations solely under inflammation or pathological conditions. LCs, as essential elements of the skin immune system, primarily function in immunological surveillance and antigen presentation. These actions are essential for sustaining skin barrier integrity, regulating immunological homeostasis, and inhibiting viral dissemination ( 39 , 40 ). Furthermore, numerous foam-like macrophages have been observed in acne lesions, and these cells have been found to express TREM2. Tran H Do demonstrated the specific overexpression of TREM2 in macrophages within acne lesions using single-cell and spatial RNA sequencing technologies, along with ultra-high-resolution Seq-Scope analysis of early acne lesions on the back skin ( 41 ). TREM2+ macrophages cannot be simply classified into the traditional M1 or M2 macrophage subsets. They represent a subset of macrophages that emerge in specific disease microenvironments and exhibit unique metabolic and functional characteristics. In acne lesions, macrophages upregulate the expression of TREM2-related genes following the phagocytosis of excess squalene, thereby differentiating into TREM2+ macrophages ( 41 ). Although TREM2+ macrophages cannot be simply classified into the M1 or M2 macrophage subsets, Tran H Do et al. found through RNA velocity analysis and pseudotime analysis that part of the TREM2+ macrophages in acne lesions differentiate from M2-like macrophages and partially overlap with M2 macrophages on the polarized continuum. This suggests that TREM2+ macrophages in acne are not a completely distinct new subtype from M2 macrophages, but rather disease-specific macrophages that overlay strong lipid metabolism and pro-inflammatory characteristics onto the M2 macrophage phenotype. Furthermore, the study also noted that there is no clear differentiation pathway between TREM2 macrophages and M1-like macrophages ( 41 ). Tissue-resident macrophages surveil the skin microenvironment to detect and eradicate infections and aberrant cells. Under steady-state conditions, these macrophages generally display an M2 phenotype, performing anti-inflammatory and tissue-repair functions to sustain skin homeostasis. However, in response to inflammatory or damage stimuli, these cell can transition to M1 phenotype to engage in inflammatory responses ( 42 ). Tissue-resident and infiltrating macrophages collaborate through mutual coordination and functional complementarity to maintain homeostasis in the skin tissue environment. Collectively, they maintain skin immunological homeostasis, protect against pathogen incursion, and facilitate tissue regeneration. 2.2 Polarization of macrophages The remarkable plasticity of macrophages is essential for their function in the skin. Macrophage plasticity refers to the ability of macrophages to dynamically adjust their phenotype and function in response to changes in their microenvironment (such as different cytokines, pathogen signals, metabolites, and activated lymphocytes) ( 43 , 44 ). The process by which macrophages activate different signaling pathways in response to specific environmental stimuli and thereby differentiate into different subsets is known as macrophage polarization, which demonstrates the plasticity of macrophages. Macrophages may typically be polarized into two distinct types: classically activated M1 macrophages and alternately activated M2 macrophages ( 45 ). Lipopolysaccharide (LPS), interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF-α) typically mediate the classical activation pathway, polarizing macrophages toward the M1 phenotype. This occurs through the production of high levels of proinflammatory factors (interleukin (IL)-1β, IL-12, IL-23, iNOS, TNF-α, monocyte chemotactic protein-1, and cytotoxic mediators [reactive oxygen species (ROS) and reactive nitrogen species(RNS)], thereby augmenting inflammation and eradicating pathogens ( 46 , 47 ). M2 activation occurs in response to stimulation of IL-4, IL-10, and IL-13. M2 macrophages, characterized as anti-inflammatory and reparative cells, are vital for suppressing inflammatory responses, enhancing tissue repair, and facilitating wound healing. Conversely, M2 macrophages predominantly manifest their anti-inflammatory properties via the upregulation of anti-inflammatory mediators, including IL-10, IL-6, prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene 6 (TSG-6), interleukin receptor antagonist (IL-RA), indoleamine 2,3-dioxygenase, and nitric oxide ( 48 , 49 ). Their function in facilitating tissue repair and wound healing predominantly depends on the secretion of several growth factors, such as transforming growth factor-β (TGF-β), platelet-derived growth factor, and vascular endothelial growth factor (VEGF). These factors stimulate fibroblast proliferation, enhance collagen production, and facilitate neovascularization, hence expediting tissue regeneration and repair processes ( 50 , 51 ). By contrast, M1 macrophages inhibit fibrosis by degrading collagen through high expression of matrix metalloproteinases (MMPs) ( 52 ). The rapid advancement of single-cell sequencing technology has facilitated a deeper exploration of macrophage heterogeneity and plasticity, challenging the traditional view that macrophages can be simply classified into M1 and M2 subtypes ( 53 – 57 ). Increasing evidence suggests that M2 macrophages encompass a diverse range of macrophages with significant biochemical and physiological differences ( 46 , 55 , 57 – 63 ). The simplistic classification of all such cells as M2 macrophages is overly broad; it obscures the heterogeneity among different types of M2 macrophages and fails to meet the standards of precision medicine ( 38 , 57 ). Thus, M2 can be further categorized into four specific subtypes: M2a, M2b, M2c, and M2d. These subtypes vary in Inducing factors, surface indicators, secreted cytokines, and biological roles. M2a, also called wound-healing macrophages, differentiate following stimulation by IL-4 and IL-13. They are characterized by high expression of CD206, CD163, and IL-1R and secrete IL-10, TGF-β, insulin-like growth factor (IGF), and IL-RA, thereby exerting anti-inflammatory, tissue repair, wound healing, antiparasitic, and pro-fibrotic effects. M2b, also called regulatory macrophages, differentiate following stimulation by immune complexes (ICs), LPS, and IL-1β. They are characterized by high expression of CD86 and major histocompatibility complex (MHC)-II and secrete IL-6, IL-1β, TNF-α, and IL-10, thereby promoting infection and tumor progression by modulating immune and inflammatory responses. M2c, also known as inactivated macrophages, differentiate following induction by IL-10, glucocorticoids, and TGF-β. They are characterized by high expression of CD206, CD163, and MerTK, and secrete TGF-β, IL-RA, and IL-10, thereby performing functions such as phagocytosis of apoptotic cells, anti-inflammation, and immunosuppression. M2d, also called tumor-associated macrophages, differentiate following stimulation by Toll-like receptors (TLR) agonists, adenosine, and IL-6. They are characterized by high expression of CD206, CD163, and VEGFR2 and secrete IL-10, VEGF, and TGF-β, thereby promoting angiogenesis, tumor growth, and metastasis ( 46 , 55 , 59 – 61 , 63 ). ( Figure 1 ) summarizes the distinct biological characteristics of M1 and these four M2. Among these four M2 subtypes, the ones we often refer to as being polarized by IL-4/13 are M2a macrophages. Additionally, David M. Mosser proposed a novel classification framework based on the three fundamental functions of macrophages—host defense, wound healing, and immune regulation—analogous to the three primary colors ( 38 ). Figure 1 This figure shows the polarization of macrophages. Macrophages can differentiate into M1 and four M2 phenotypes under different microenvironmental stimuli. M1 predominantly performs host defense, antibacterial, and anticancer functions via proinflammatory actions; however, excessive activation may hasten the progression of chronic inflammation or autoimmune disorders. M2a is integral to anti-inflammatory responses, tissue repair, wound healing, antiparasitism, and fibrosis; M2b facilitates infection and tumor progression through the modulation of
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