Major thermal injury induces a pathophysiological response that has a marked inflammatory/immune component which contributes to numerous complications that include delayed wound healing, increased susceptibility to sepsis and multiple organ failure. A wide range of mediators and cell types closely regulate the post-burn inflammatory process. Nonetheless, the ability of the burn patient to maintain an appropriate balance between inflammatory and anti-inflammatory responses following major burn injury is often disrupted leading to immunopathological complications. In this regard, a unique T-cell subset, gamma delta (7/8) T- cells has the ability to regulate inflammatory and healing processes. Gamma/delta T-cells are likely to be a critical component of the patient's successful recovery from burn injury. Our recent findings support an important multi-faceted role for y/8 T-cells in post-burn immunopathology by demonstrating the following: they are mobilized and activated early post-injury;they regulate post-burn neutrophil migration and;7/8 T- cells contribute to burn wound healing via the regulation of growth factor, cytokine, and nitric oxide (NO) production at the injury site. While macrophage NO production (which is regulated by y/8 T-cells under certain conditions) is an important mediator of post-burn immune dysfunction, it is also critical to many aspects of wound repair. Burn injury is first and foremost an injury to the skin and a vast majority of burn patients have complications related to healing of the burn or skin graft site. Nonetheless, while y/8 T-cells are important to wound healing, their role in such processes post-burn remains to be clearly elucidated. It is our hypothesis that y/8 T-cells play a critical regulatory role in the post-burn dermal inflammatory response and wound healing that is, in part, mediated by an iNOS-dependent mechanism.
The specific aims will determine: 1) the role of y/8 T-cells in post-burn wound healing and the dermal inflammatory response;2) the role of y/8 T-cells in burn excision and grafting and;3) the relationship of y/8 T-cells to the post burn wound healing and inflammatory responses in humans. Elucidation of the relationships between y/8 T-cells, the dermal inflammatory response and post-burn wound healing will be vital in the development of improved therapeutic regimes for this critically ill patient population, which could include the novel concept of biotherapy with y/8 T-cells or modulation of native y/8 T-cell activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079122-05
Application #
8133493
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
2007-09-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$248,882
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Surgery
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Rani, Meenakshi; Nicholson, Susannah E; Zhang, Qiong et al. (2017) Damage-associated molecular patterns (DAMPs) released after burn are associated with inflammation and monocyte activation. Burns 43:297-303
Rani, Meenakshi; Schwacha, Martin G (2017) The composition of T-cell subsets are altered in the burn wound early after injury. PLoS One 12:e0179015
Schwacha, Martin G; Rani, Meenakshi; Nicholson, Susannah E et al. (2016) Dermal ?? T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns. PLoS One 11:e0158993
Rani, Meenakshi; Zhang, Qiong; Scherer, Michael R et al. (2015) Activated skin ?? T-cells regulate T-cell infiltration of the wound site after burn. Innate Immun 21:140-50
Rani, Meenakshi; Zhang, Qiong; Schwacha, Martin G (2014) Burn wound ?? T-cells support a Th2 and Th17 immune response. J Burn Care Res 35:46-53
Rani, Meenakshi; Zhang, Qiong; Schwacha, Martin G (2014) Gamma delta T cells regulate wound myeloid cell activity after burn. Shock 42:133-41
Schwacha, Martin G; Rani, Meenakshi; Zhang, Qiong et al. (2014) Mitochondrial damage-associated molecular patterns activate ?? T-cells. Innate Immun 20:261-8
Rani, Meenakshi; Schwacha, Martin G (2012) Aging and the pathogenic response to burn. Aging Dis 3:171-80
Oppeltz, Richard F; Rani, Meenakshi; Zhang, Qiong et al. (2012) Gamma delta (ýýýý) T-cells are critical in the up-regulation of inducible nitric oxide synthase at the burn wound site. Cytokine 60:528-34
Sasaki, Jennifer R; Zhang, Qiong; Schwacha, Martin G (2011) Burn induces a Th-17 inflammatory response at the injury site. Burns 37:646-51

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