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Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2026, vol. 32, issue2
Subject Area: Medicine
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DOI: 10.5272/jimab.2026322.6928
Published online: 23 June 2026
Review article
J of IMAB. 2026 Apr-Jun;32(2):6928-6936
ROLE OF IMMUNE CELLS IN WOUND HEALING: A MINI-REVIEW
Minka Hristova
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Department of Physiology and Pathophysiology, Medical University of Varna, Bulgaria.
ABSTRACT:
The skin is the largest anatomical organ in the human body and performs many physiological functions. Protection of the body from harmful environmental influences is among the main functions of the skin. Skin wounds initiate a protective programme to restore tissue integrity and maintain the homeostasis of the body. This process occurs in four consecutive phases: haemostasis, inflammation, proliferation, and tissue remodelling. Different types of cells participate, among which immune cells play a key role. The complex interactions between these cells and the extracellular matrix ensure the physiological course of tissue healing. The purpose of this review is to present the skin as a protective organ and to describe the involvement of immune cells, specifically granulocytes and mononuclear cells, in the distinct stages of wound healing.
Keywords: skin; skin protection; wound healing; immune cells,
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Please cite this article as: Hristova M. Role of immune cells in wound healing: a mini-review. J of IMAB. 2026 Apr-Jun;32(2):6928-6936. [Crossref - 10.5272/jimab.2026322.6928]
Correspondence to: Minka Hristova Aleksandrova, Department of Physiology and Pathophysiology, Faculty of Medicine, Medical University of Varna; 55, Marin Drinov Str., 9002 Varna, Bulgaria. E-mail: hristova.minka@abv.bg
REFERENCES:
1. Dąbrowska AK, Spano F, Derler S, Adlhart C, Spencer ND, Rossi RM. The relationship between skin function, barrier properties, and body-dependent factors. Skin Res Technol. 2018 May;24(2):165-174. [Crossref]
2. McKnight G, Shah J, Hargest R. Physiology of the skin. Surgery (Oxford). 2022 Jan;40(1):8-12. [Crossref]
3. Beldon P. The skin – the body's defence mechanism. Wound Essentials. 2010; 5:112-114. [Internet]
4. Schilrreff P, Alexiev U. Chronic Inflammation in Non-Healing Skin Wounds and Promising Natural Bioactive Compounds Treatment. Int J Mol Sci. 2022 Apr 28;23(9):4928. [PubMed]
5. Mohamed SA, Hargest R. Surgical Anatomy of the Skin. Surgery (Oxford). 2022 Jan;40(1):1-7. [Crossref]
6. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound Healing: A Cellular Perspective. Physiol Rev. 2019 Jan 1;99(1):665-706. [Crossref]
7. Sim SL, Kumari S, Kaur S, Khosrotehrani K. Macrophages in Skin Wounds: Functions and Therapeutic Potential. Biomolecules. 2022 Nov 8;12(11):1659. [Crossref]
8. Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol. 2002 Jul-Aug;12(4):390-9. [PubMed]
9. Cioce A, Cavani A, Cattani C, Scopelliti F. Role of the Skin Immune System in Wound Healing. Cells. 2024 Apr 4;13(7):624. [Crossref]
10. Del Rosso JQ, Levin J. The clinical relevance of maintaining the functional integrity of the stratum corneum in both healthy and disease-affected skin. J Clin Aesthet Dermatol. 2011 Sep;4(9):22-42. [PubMed]
11. Rosso JD, Zeichner J, Alexis A, Cohen D, Berson D. Understanding the Epidermal Barrier in Healthy and Compromised Skin: Clinically Relevant Information for the Dermatology Practitioner: Proceedings of an Expert Panel Roundtable Meeting. J Clin Aesthet Dermatol. 2016 Apr;9(4 Suppl 1):S2-S8. [PubMed]
12. Sussman G. An update on wound management. Aust Prescr. 2023 Aug;46(2):29-35. [Crossref]
13. Chhabra S, Chhabra N, Kaur A, Gupta N. Wound Healing Concepts in Clinical Practice of OMFS. J Maxillofac Oral Surg. 2017 Dec;16(4):403-423. [Crossref]
14. Sulakhiya K, Soni P, Tembhre MK, Kungumaraj HJ, Paliwal R, Kumar S. 2 - Physiology and pharmacology of wounds. In: Nanotechnological Aspects for Next-Generation Wound Management. Solanki PR, Kumar A, Singh RP, Singh J, Singh KRB. (Eds.) Academic Press. 2024; Chapter 2, pp.21-54 [Crossref]
15. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009 Sep-Oct;37(5):1528-42. [Crossref]
16. Phillipson M, Kubes P. The Healing Power of Neutrophils. Trends Immunol. 2019 Jul;40(7):635-647. [Crossref]
17. Martin P, Nunan R. Cellular and molecular mechanisms of repair in acute and chronic wound healing. Br J Dermatol. 2015 Aug;173(2):370-8. [Crossref]
18. Aitcheson SM, Frentiu FD, Hurn SE, Edwards K, Murray RZ. Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds. Molecules. 2021 Aug 13;26(16):4917. [Crossref]
19. Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of Acute and Chronic Wound Healing. Biomolecules. 2021 May 8;11(5):700. [Crossref]
20. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010 Mar;89(3):219-29. [PubMed]
21. Wilgus TA, Roy S, McDaniel JC. Neutrophils and Wound Repair: Positive Actions and Negative Reactions. Adv Wound Care (New Rochelle). 2013 Sep;2(7):379-388. [Crossref]
22. Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing. J Leukoc Biol. 2001 Apr;69(4):513-21. [Crossref]
23. Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front Physiol. 2018 Feb 20;9:113. [Crossref]
24. Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. J Athl Train. 2006 Oct-Dec;41(4):457-65. [PubMed]
25. Su Y, Richmond A. Chemokine Regulation of Neutrophil Infiltration of Skin Wounds. Adv Wound Care (New Rochelle). 2015 Nov 1;4(11):631-640. [Crossref]
26. Wen T, Rothenberg ME. The Regulatory Function of Eosinophils. Microbiol Spectr. 2016 Oct 30;4(5):MCHD-0020-2015. [Crossref]
27. Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, et al. Eosinophils from Physiology to Disease: A Comprehensive Review. Biomed Res Int. 2018 Jan 28;2018:9095275. [Crossref]
28. Sastre B, Rodrigo-Muñoz JM, Garcia-Sanchez DA, Cañas JA, Del Pozo V. Eosinophils: Old Players in a New Game. J Investig Allergol Clin Immunol. 2018;28(5):289-304. [Crossref]
29. Wong DT, Donoff RB, Yang J, Song BZ, Matossian K, Nagura N, et al. Sequential expression of transforming growth factors alpha and beta 1 by eosinophils during cutaneous wound healing in the hamster. Am J Pathol. 1993 Jul;143(1):130-42. [PubMed]
30. Zeinoun T, Aftimos G, Bou Saba S, Nammour S. Eosinophils and mastocytes in healing laser excision wounds. Lasers Med Sci. 2009 May;24(3):307-12. [Crossref]
31. Song BZ, Donoff RB, Tsuji T, Todd R, Gallagher GT, Wong DT. Identification of rabbit eosinophils and heterophils in cutaneous healing wounds. Histochem J. 1993 Oct;25(10):762-71. [Crossref]
32. Todd R, Donoff BR, Chiang T, Chou MY, Elovic A, Gallagher GT, et al. The eosinophil as a cellular source of transforming growth factor alpha in healing cutaneous wounds. Am J Pathol. 1991 Jun;138(6):1307-13. [PubMed]
33. Hibbs MS, Mainardi CL, Kang AH. Type-specific collagen degradation by eosinophils. Biochem J. 1982 Dec 1;207(3):621-4. [Crossref]
34. Yang J, Torio A, Donoff RB, Gallagher GT, Egan R, Weller PF, et al. Depletion of eosinophil infiltration by anti-IL-5 monoclonal antibody (TRFK-5) accelerates open skin wound epithelial closure. Am J Pathol. 1997 Sep;151(3):813-9. [PubMed]
35. Leitch VD, Strudwick XL, Matthaei KI, Dent LA, Cowin AJ. IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation. Immunol Cell Biol. 2009 Feb;87(2):131-40. [Crossref]
36. Enoch S, Price P. Cellular, molecular and biochemical differences in the pathophysiology of healing between acute wounds, chronic wounds and wounds in the aged. World Wide Wounds. 2005. [Internet]
37. Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. 2018 May 1;9:419. [Crossref]
38. Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med. 2011 Jul 11;13:e23. [Crossref]
39. Gurevich DB, Severn CE, Twomey C, Greenhough A, Cash J, Toye AM, et al. Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression. EMBO J. 2018 Jul 2;37(13):e97786. [Crossref]
40. Joorabloo A. Liu T. Recent advances in nanomedicines for regulation of macrophages in wound healing. J Nanobiotechnol. 2022, 20, 407. [Crossref]
41. Strbo N, Yin N, Stojadinovic O. Innate and Adaptive Immune Responses in Wound Epithelialization. Adv Wound Care (New Rochelle). 2014 Jul 1;3(7):492-501. [Crossref]
42. Wang X, Balaji S, Steen EH, Li H, Rae MM, Blum AJ, et al. T Lymphocytes Attenuate Dermal Scarring by Regulating Inflammation, Neovascularisation, and Extracellular Matrix Remodeling. Adv Wound Care (New Rochelle). 2019 Nov 1;8(11):527-537. [PubMed]
43. Short WD, Wang X, Keswani SG. The Role of T Lymphocytes in Cutaneous Scarring. Adv Wound Care (New Rochelle). 2022 Mar;11(3):121-131. [Crossref]
44. Fishel RS, Barbul A, Beschorner WE, Wasserkrug HL, Efron G. Lymphocyte participation in wound healing. Morphologic assessment using monoclonal antibodies. Ann Surg. 1987 Jul;206(1):25-9. [Crossref]
45. Efron JE, Frankel HL, Lazarou SA, Wasserkrug HL, Barbul A. Wound healing and T-lymphocytes. J Surg Res. 1990 May;48(5):460-3. [Crossref]
46. Schäffer M, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg. 1998 Apr;85(4):444-60. [Crossref]
47. Chen L, Mehta ND, Zhao Y, DiPietro LA. Absence of CD4 or CD8 lymphocytes changes infiltration of inflammatory cells and profiles of cytokine expression in skin wounds, but does not impair healing. Exp Dermatol. 2014 Mar;23(3):189-94. [Crossref]
48. Allen HC, Sharma P. Histology, Plasma Cells. [Updated 2022 Dec 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2025 Jan-. [PubMed]
49. Karaaslan S, Tomayko MM. A Niche for Plasma Cells: The Skin. J Invest Dermatol. 2019 Dec;139(12):2411-2414. [Crossref]
50. Wilson RP, McGettigan SE, Dang VD, Kumar A, Cancro MP, Nikbakht N, et al. IgM Plasma Cells Reside in Healthy Skin and Accumulate with Chronic Inflammation. J Invest Dermatol. 2019 Dec;139(12):2477-2487. [Crossref]
51. Loots MA, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol. 1998 Nov;111(5):850-7. [Crossref]
52. Iwata Y, Yoshizaki A, Komura K, Shimizu K, Ogawa F, Hara T, et al. CD19, a response regulator of B lymphocytes, regulates wound healing through hyaluronan-induced TLR4 signaling. Am J Pathol. 2009 Aug;175(2): 649–660. [Crossref]
53. Sîrbulescu RF, Boehm CK, Soon E, Wilks MQ, Ilieş I, Yuan H, et al. Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions. Wound Repair Regen. 2017 Sep;25(5):774-791. [Crossref]
54. Nishio N, Ito S, Suzuki H, Isobe K. Antibodies to wounded tissue enhance cutaneous wound healing. Immunology. 2009 Nov;128(3): 369–380. [Crossref]
55. Nishio N, Ito S, Suzuki H, Okawa Y, Isobe K. Effect of Aging on Auto-Antibodies to Wounded Tissues. The Open Geriat Med J. 2010, 3, 17-24. [Crossref]
56. Syrjänen SM, Syrjänen KJ. Plasma cells and their immunoglobulins in the normal and delayed healing of the extraction wound in man. Br J Oral Surg. 1980 Sep;18(2): 100–106. [Crossref]
57. Iskandar RPD, Indrawati R, Arundina I, Rahayu RP. The amount of macrophages and activated plasma cells on wound healing process affected by spirulina. Dent. J. (Majalah Kedokteran Gigi). 2015;48:209–212. [Crossref]
58. Veličković V, Janković D. Challenges around quantifying uncertainty in a holistic approach to hard-to-heal wound management: Health economic perspective. Int Wound J. 2023 Mar;20(3):792-798. [Crossref]
59. Kaushik D, Xu B, Kumar M. Biomarkers in immunology: Their impact on immune function and response. ABST. 2025; 7:95-110. [Crossref]
60. Fahimirad S, Fattahi F, Hatami M, Shabani S, Ghorbanpour M. Nanotechnology-based biotherapeutics for physiological wound healing phases. Industrial Crops and Products. 2025; 226, 120608, ISSN 0926-6690. [Crossref]
61. Monavari M, Sohrabi R, Motasadizadeh H, Monavari M, Fatahi Y, Ejarestaghi NM, et al. Levofloxacin loaded poly (ethylene oxide)-chitosan/quercetin loaded poly (D,L-lactide-co-glycolide) core-shell electrospun nanofibers for burn wound healing. Front Bioeng Biotechnol. 2024 Mar 28;12:1352717. [Crossref]
62. Sajjad A, Ali H, Zia M. Fabrication and evaluation of vitamin doped Zno/AgNPs nanocomposite based wheat gluten films: a promising findings for burn wound treatment. Sci Rep. 2023 Sep 26;13(1):16072. [PubMed]
63. Gao M, Guo H, Dong X, Wang Z, Yang Z, Shang Q, et al. Regulation of inflammation during wound healing: the function of mesenchymal stem cells and strategies for therapeutic enhancement. Front Pharmacol. 2024 Feb 15;15:1345779. [Crossref]
64. Tang Q, Dong M, Xu Z, Xue N, Jiang R, Wei X, et al. Red blood cell-mimicking liposomes loading curcumin promote diabetic wound healing. J Control Release. 2023 Sep;361:871-884. [Crossref]
65. Li H, Xu L, Chen J, Huang H, Liang F, Li S, et al. Neutrophil Extracellular Trap Formation Suppressed by Ro 106-9920 Enhances Diabetic Wound Healing by Blocking NLRP3 Inflammasome Activation. Front Biosci (Landmark Ed). 2025 May 19;30(5):37393. [Crossref]
66. López-Cuevas P, Oates TCL, Tong Q, McGowan LM, Cross SJ, Xu C, et al. Reprogramming macrophages with R848-loaded artificial protocells to modulate skin and skeletal wound healing. J Cell Sci. 2024 Aug 15;137(16):jcs262202. [Crossref]
Received: 21 October 2025
Published online: 23 June 2026