Compartmentalized control of skin immunity by resident commensals.

Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y. Compartmentalized control of skin immunity by resident commensals. Science. 337(6098):1115-9 Jul, 2012

Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease

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GATA3 controls Foxp3⁺ regulatory T cell fate during inflammation in mice.

Wohlfert EA, Grainger JR, Bouladoux N, Konkel JE, Oldenhove G, Ribeiro CH, Hall JA, Yagi R, Naik S, Bhairavabhotla R, Paul WE, Bosselut R, Wei G, Zhao K, Oukka M, Zhu J, Belkaid Y. GATA3 controls Foxp3⁺ regulatory T cell fate during inflammation in mice. J Clin Invest. 121(11):4503-15 Nov, 2011

Our data indicate that GATA3 limits Treg polarization toward an effector T cell phenotype and acquisition of effector cytokines in inflamed tissues. Overall, our work reveals what we believe to be a new facet in the complex role of GATA3 in T cells and highlights what may be a fundamental role in controlling Treg physiology during inflammation.

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Essential Role for Retinoic acid in promotion of CD4+ T cell responses via retinoic receptor alpha

Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, Wohlfert EA, Chou DB, Oldenhove G, Robinson M, Grigg ME, Kastenmayer R, Schwartzberg PL, Belkaid Y. Essential Role for Retinoic acid in promotion of CD4+ T cell responses via retinoic receptor alpha. Immunity. 34(3):435-47 March, 2011

Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4+ helper T cell responses to infection and mucosal vaccination.

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Severe tissue trauma triggers the autoimmune state systemic lupus erythematous in the MRL/++ lupus prone mice.

Anam K, Amare M, Naik S, and Davis TA. Severe tissue trauma triggers the autoimmune state systemic lupus erythematous in the MRL/++ lupus prone mice. Lupus. 18(4):318-31 April, 2009

Tissue damage associated with a severe injury can result in profound inflammatory responses that may trigger autoimmune development in lupus-prone individuals. In this study, we investigated the role of a large full-thickness cutaneous burn injury on the early onset of autoimmune disease in lupus-prone MRL/++ mice.

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Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to severe cutaneous burn injury

Davis TA, Stojadinovic A, Anam K, Melissa K, Amare M, Naik S, Peoples GE, Tadaki D, and Elester EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to severe cutaneous burn injury. International Wound Journal. 6(1):11-21 Feb, 2009

Following severe burn injury, persistent inflammation perpetuated by surface eschar, bacterial colonisation and neutrophil proteolytic activity can impede normal healing and result in further tissue damage. Extracorporeal shock wave treatment (ESWT) has been shown in the clinical setting to promote the healing of burn and difficult‐to‐heal wounds; however, the mechanism is unclear. We investigated the role of ESWT on the early proinflammatory response using a severe, full‐thickness and highly inflammatory cutaneous burn wound in a murine model.

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