Skin Resident γδ T Cell Function and Regulation in Wound Repair

Munoz, Luis D; Sweeney, Michael; Jameson, Julie

doi:10.3390/ijms21239286

Cited by 36 publications

(36 citation statements)

References 125 publications

(248 reference statements)

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“…Recently, lymphocytes have been highlighted as important cells that regulate wound healing responses. 6 – 8 We demonstrated a role for lymphocytes, specifically CD4 + lymphocytes, in regulation of dermal fibrosis in the severe combined immune deficient (SCID) mouse model. 9 Of the CD4 + subtypes, two immunoregulatory subsets stand out as producers of IL-10, CD4 + Foxp3 + regulatory T cells (Treg) which also produce transforming growth factor (TGF)-β and CD4 + Foxp3 - CD49b + Lag3 + type 1 regulatory T cells (Tr1) which additionally produce TGF-β, IFN-γ, and low levels of IL-4.…”

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confidence: 99%

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

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Wang

et al. 2021

Annals of Surgery

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Objective: Demonstrate the impact of IL-10 producing T lymphocytes on mediating dermal scarring. Summary Background Data: We demonstrated that CD4 + cells are essential to improving postinjury wound healing and preventing fibrosis. CD4 + subsets secrete differential cytokine and growth factor profiles, though their role in fibrosis is not known. IL-10, a key anti-inflammatory cytokine shown to promote regenerative wound healing, is secreted by some CD4 + subsets. We, therefore, hypothesize that IL-10 producing CD4 + T lymphocyte subsets selectively attenuate dermal wound fibrosis. Methods: IL-10 -/- and wild-type murine splenocytes were enriched for CD4 + lymphocytes and adoptively transferred into severe combined immunodeficient (SCID) mice that received full-thickness wounds which were analyzed at days 7 and 28 for inflammation and collagen content. We then sorted CD4 + CD44 int/low FoxP3 - CD62L + T cells (Tnaive) or CD4 + CD44 Hi FoxP3 - type 1 regulatory (Tr1) T cell subsets from 10BiT murine splenocytes, activated them, and transferred them into wounds. In vitro , dermal fibroblasts were cocultured with Tnaive or Tr1 and the effect on extracellular matrix (ECM) regulation was analyzed. Results: The anti-inflammatory and antifibrotic effects of CD4 + cells on SCID wounds were lost with cells from IL-10 -/- mice. Adoptive transfer of Tr1 into SCID mice resulted in accelerated wound closure at d7 with reduced fibrosis at d28, with Tr1 favoring hyaluronan production by fibroblasts, an ECM molecule implicated in IL-10-induced regenerative healing. Conclusions: IL-10 producing T-lymphocytes, specifically Tr1, regulate inflammatory cell cytokine expression to promote HA-rich ECM deposition and attenuate fibrosis. Promoting IL-10 producing lymphocytes in wounds may be a therapeutic target to promote regenerative wound healing.

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confidence: 99%

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

Short

Wang

et al. 2021

Annals of Surgery

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“…The situation is made more complicated by the existence of unconventional γδ T cells, which are very abundant in skin [80]. The lack of skin γδ T cells is associated with late wound resolution and decreased inflammation [81]. Thus, the exact role of T cells in acute wound healing remains complex.…”

Section: Adaptive Immunity In Acute Wound Healingmentioning

confidence: 99%

“…Besides conventional alpha beta T cells, γδ T cells take part in inflammatory response during wound healing. Specifically, they recognize DAMPs and secrete IL-17 and IL-22, which further promote inflammation [81].…”

Section: Adaptive Immunity In Acute Wound Healingmentioning

confidence: 99%

“…T cells also take part in the later stages of wound healing, including re-epithelization and remodeling. In particular, γδ T cells release IGF-1, which promotes keratinocyte survival and proliferation [80,81]. Furthermore, T cells facilitate polarization of antiinflammatory macrophages, which in turn suppress inflammation and stimulate ECM deposition, angiogenesis and tissue repair [7].…”

Section: Adaptive Immunity In Acute Wound Healingmentioning

confidence: 99%

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Immunology of Acute and Chronic Wound Healing

et al. 2021

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Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

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“…Recent work conducted in mice indicates the synergistic involvement of IL-1α and IL-7, secreted by keratinocytes, in the expansion of epidermal γδ T cells ( 177 ). γδ T cells are resident epidermal cells, which upon activation secrete KGF and induce the proliferation of epidermal stem cells ( 178 , 179 ). Moreover, it has been shown that in mice IL-1β is indispensable in the recall of inflammatory memory of epidermal stem cells, facilitating wound healing following repeated insults ( 180 ).…”

Section: Il-1 Family Cytokines In the Promotion Of Wound Healingmentioning

confidence: 99%

The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

et al. 2021

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The skin barrier would not function without IL-1 family members, but their physiological role in the immunological aspects of skin barrier function are often overlooked. This review summarises the role of IL-1 family cytokines (IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37 and IL-38) in the skin. We focus on novel aspects of their interaction with commensals and pathogens, the important impact of proteases on cytokine activity, on healing responses and inflammation limiting mechanisms. We discuss IL-1 family cytokines in the context of IL-4/IL-13 and IL-23/IL-17 axis-driven diseases and highlight consequences of human loss/gain of function mutations in activating or inhibitory pathway molecules. This review highlights recent findings that emphasize the importance of IL-1 family cytokines in both physiological and pathological cutaneous inflammation and emergent translational therapeutics that are helping further elucidate these cytokines.

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Skin Resident γδ T Cell Function and Regulation in Wound Repair

Cited by 36 publications

References 125 publications

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

Interleukin-10 Producing T Lymphocytes Attenuate Dermal Scarring

Immunology of Acute and Chronic Wound Healing

The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

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