Toward Understanding Wound Immunology for High-Fidelity Skin Regeneration

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2022 Jun 6

PMID 35667792

Authors

Yingchao Xue

Sashank K Reddy

Luis A Garza

Affiliations

Soon will be listed here.

Abstract

Effective tissue repair is vital for the survival of organisms. Yet, how the immune system coordinates with tissue stem cells (SCs) to effect postnatal tissue restoration remains elusive. This review presents current knowledge surrounding wound-induced SC and immune signaling that favors tissue repair, including wound healing and regeneration. We discuss factors that affect regenerative capacities among organisms and the dynamics of local immune cells and SCs during reepithelialization. We also present recent insights into how immune niches communicate with SCs or other body systems to restore the epithelial architecture. Additionally, we summarize our findings on functional wound regeneration, specifically how alarmin (double-stranded RNA [dsRNA])-activated Toll-like receptor signaling and host-microbe interaction-related immune pathways alter the regenerative property of skin SCs. Last, we touch on mechanisms by which known immunologic cellular and molecular signaling might boost the skin's regenerative property. Overall, this review will provide insights into how therapeutically modulating immune signaling could enhance postnatal tissue regeneration.

Citing Articles

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Biyashev D, Siwicka Z, Onay U, Demczuk M, Xu D, Ernst M NPJ Regen Med. 2023; 8(1):61.

PMID: 37919305 PMC: 10622536. DOI: 10.1038/s41536-023-00331-1.

References

Mascharak S, desJardins-Park H, Davitt M, Griffin M, Borrelli M, Moore A . Preventing activation in fibroblasts yields wound regeneration without scarring. Science. 2021; 372(6540). PMC: 9008875. DOI: 10.1126/science.aba2374. View

McCusker C, Bryant S, Gardiner D . The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods. Regeneration (Oxf). 2016; 2(2):54-71. PMC: 4895312. DOI: 10.1002/reg2.32. View

Toyoshima K, Asakawa K, Ishibashi N, Toki H, Ogawa M, Hasegawa T . Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nat Commun. 2012; 3:784. PMC: 3337983. DOI: 10.1038/ncomms1784. View

Gay D, Kwon O, Zhang Z, Spata M, Plikus M, Holler P . Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding. Nat Med. 2013; 19(7):916-23. PMC: 4054871. DOI: 10.1038/nm.3181. View

Fullgrabe A, Joost S, Are A, Jacob T, Sivan U, Haegebarth A . Dynamics of Lgr6⁺ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis. Stem Cell Reports. 2015; 5(5):843-855. PMC: 4649262. DOI: 10.1016/j.stemcr.2015.09.013. View

Sirbulescu R, Boehm C, Soon E, Wilks M, Ilies I, Yuan H . Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions. Wound Repair Regen. 2017; 25(5):774-791. PMC: 5760362. DOI: 10.1111/wrr.12584. View

Breedis C . Regeneration of hair follicles and sebaceous glands from the epithelium of scars in the rabbit. Cancer Res. 1954; 14(8):575-9. View

Kim D, Hossain M, Nieves A, Gu L, Ratliff T, Oh S . To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease. Am J Pathol. 2016; 186(5):1140-50. PMC: 4861769. DOI: 10.1016/j.ajpath.2015.12.030. View

Huang S, Kuri P, Aubert Y, Brewster M, Li N, Farrelly O . Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. Cell Stem Cell. 2021; 28(9):1582-1596.e6. PMC: 8528178. DOI: 10.1016/j.stem.2021.05.007. View

10.

Rognoni E, Gomez C, Pisco A, Rawlins E, Simons B, Watt F . Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing. Development. 2016; 143(14):2522-35. PMC: 4958333. DOI: 10.1242/dev.131797. View

11.

Nelson A, Loy D, Lawson J, Katseff A, FitzGerald G, Garza L . Prostaglandin D2 inhibits wound-induced hair follicle neogenesis through the receptor, Gpr44. J Invest Dermatol. 2012; 133(4):881-9. PMC: 3593761. DOI: 10.1038/jid.2012.398. View

12.

Joost S, Annusver K, Jacob T, Sun X, Dalessandri T, Sivan U . The Molecular Anatomy of Mouse Skin during Hair Growth and Rest. Cell Stem Cell. 2020; 26(3):441-457.e7. DOI: 10.1016/j.stem.2020.01.012. View

13.

Eming S, Wynn T, Martin P . Inflammation and metabolism in tissue repair and regeneration. Science. 2017; 356(6342):1026-1030. DOI: 10.1126/science.aam7928. View

14.

Horne K, Jahoda C, Oliver R . Whisker growth induced by implantation of cultured vibrissa dermal papilla cells in the adult rat. J Embryol Exp Morphol. 1986; 97:111-24. View

15.

Nelson A, Reddy S, Ratliff T, Hossain M, Katseff A, Zhu A . dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell Stem Cell. 2015; 17(2):139-51. PMC: 4529957. DOI: 10.1016/j.stem.2015.07.008. View

16.

Wier E, Asada M, Wang G, Alphonse M, Li A, Hintelmann C . Neutrophil extracellular traps impair regeneration. J Cell Mol Med. 2021; 25(21):10008-10019. PMC: 8572775. DOI: 10.1111/jcmm.16896. View

17.

Liu S, Zhang H, Duan E . Epidermal development in mammals: key regulators, signals from beneath, and stem cells. Int J Mol Sci. 2013; 14(6):10869-95. PMC: 3709707. DOI: 10.3390/ijms140610869. View

18.

Shiraishi M, Shintani Y, Shintani Y, Ishida H, Saba R, Yamaguchi A . Alternatively activated macrophages determine repair of the infarcted adult murine heart. J Clin Invest. 2016; 126(6):2151-66. PMC: 4887176. DOI: 10.1172/JCI85782. View

19.

Brockes J, Kumar A, Velloso C . Regeneration as an evolutionary variable. J Anat. 2001; 199(Pt 1-2):3-11. PMC: 1594962. DOI: 10.1046/j.1469-7580.2001.19910003.x. View

20.

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; 9:419. PMC: 5938667. DOI: 10.3389/fphys.2018.00419. View