Although DC-activating signals might derive from microbes that ar

Although DC-activating signals might derive from microbes that are present in the steady state, such as commensals or subclinical infections, DC activation and autoimmunity MK-8669 order also develop upon Treg-cell depletion

in germ-free animals. This indicates that endogenous signals alone are sufficient to drive DC activation and the resulting breakdown of peripheral tolerance in the absence of Treg cells [72]. One such endogenous DC-activating signal is ligation of CD40. We have recently demonstrated that, in the absence of Treg cells, T cells activate DCs via CD40L–CD40 interactions, thus establishing a positive feedback loop, in which autoreactive T cells can drive their own activation and expansion [70]. Other endogenous DC-activating signals that can drive tolerance breakdown might include endogenous retroviruses [73], sensing of necrotic cell death [74, 75] and steady-state levels of proinflammatory cytokines. DCs stand out as the master regulators of adaptive immunity owing to their indispensable role for both naïve T-cell priming and peripheral tolerance induction. A diverse array of activating receptors allows DCs to sense hallmarks of an ongoing infection and orchestrate the immune defense. However, as discussed in

this review, negative regulation SB203580 cell line of DC activation is crucial, as it prevents breakdown of peripheral tolerance owing to the presence of danger signals in the steady state and, thus, autoimmunity (Fig. 1). Clomifene Negative regulation of DC activation is provided by Treg cells in a way that depends on cognate TCR–MHC class II interactions. Several mechanisms of the suppressive armory of Treg cells have been shown to target DCs although their individual contribution remains to be established. Similarly, there are many ways to activate a DC and the mechanisms

that contribute to DC activation and the breakdown of tolerance in the absence of Treg cells remain to be determined. The detailed understanding of the opposing influences affecting DC activation levels and behavior will be important for identifying possible misuse of regulatory mechanisms in autoimmunity, cancer, and chronic infectious diseases. The authors thank Susanne Brookshire for critically reading the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (GK 1043 to H.C.P. and H.S., PR1184/2-1 to H.C.P.), the MAIFOR program of the University Medical Center Mainz (H.C.P.), and the Immunology Research Center (FZI) Mainz. The authors declare no financial or commercial conflict of interest. “
“Names influence how something is perceived. Diagnostic terms (diagnoses) are the names of diseases that are usually derived either from some distinctive characteristic of the disease or include an eponym recognizing someone who elucidated the disease. No matter how logical and appropriate a name may be, if it is not usable and used it is of no lasting value.

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