The Jak, Tyk2, is activated in response to IL-12 and IFN-αβ and promotes IFN-γ production by Th1-type CD4 cells. Mice deficient in Tyk2 function have been previously shown to be resistant to autoimmune arthritis and septic shock but are acutely susceptible to opportunistic pathogens such as Toxoplasma gondii. In this study, we show that Tyk2, in addition to mediating the biological effects of IL-12 and IFN-αβ, is an important regulator for the signaling and expression of the immunosuppressive cytokine IL-10. In the absence of Tyk2, Ag-reactive CD4 cells exhibit impaired IL-10 synthesis following rechallenge of T. gondii vaccine-primed mice. The impaired IL-10 reactivation leads to unopposed antimicrobial effector mechanisms which results in a paradoxically superior protection of immune Tyk2−/− mice against virulent T. gondii challenge. We further demonstrate that Tyk2 indirectly controls CD4 IL-10 reactivation by signaling for maximal IFN-γ secretion. The unexpected role of IFN-γ in mediating IL-10 reactivation by Th1 cells provides compelling evidence that conditions driving Th1 responses establish a negative feedback loop, which will ultimately lead to its autoregulation. Thus, Tyk2 can be viewed as a dual-function Jak, mediating both pro and anti-inflammatory cytokine responses.

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Our study suggests patients requiring ventilator support on admission and those with bilateral injuries are at increased risk of developing RH. Early identification of patients at risk for RH may allow for earlier intervention and potential benefits to the patient.

Penetrating injuries to the thorax have the potential to disrupt two vital life-sustaining systems: the respiratory and the cardiovascular system. These injuries have the potential to be rapidly fatal and thus a rapid, organized, and logical approach to the evaluation and resuscitation of these patients is critical. This article briefly reviews the basic pathophysiology of penetrating chest wounds and the evaluation of both stable and unstable patients after penetrating chest injury. The recent literature is reviewed, including recent findings on screening for occult penetrating cardiac injuries, the use of needle decompression for pneumothoraces, and the expanding role of ultrasonography in the evaluation of penetrating thoracic trauma. Our goal is to review the initial management and resuscitation of patients with penetrating wounds to the thorax, with an eye toward the injuries most likely to rapidly result in death.