Dendritic cells at the interface of innate and acquired immunity: the role for epigenetic changes

Haitao Wen^*, Matthew A. Schaller^*, Yali Dou^*^,, Cory M. Hogaboam^* and Steven L. Kunkel^*^,1

^* Departments of Pathology and
Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA

¹Correspondence: Department of Pathology, University of Michigan Medical School, 4071 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA. E-mail: slkunkel{at}umich.edu

ABSTRACT

Dendritic cells (DC) are known to be essential immune cellsin innate immunity and in the initiation of adaptive immunity.The shaping of adaptive immunity by innate immunity is dependenton DC unique cellular functions and DC-derived effector moleculessuch as cytokines and chemokines. Thus, it is not surprisingthat numerous studies have identified alterations in DC number,function, and subset ratios in various diseases, such as infections,cancers, and autoimmune diseases. Recent evidence has also identifiedthat immunosuppression occurring after severe systemic inflammation,such as found in sepsis, is a result of depletion in DC numbersand a later dysfunction in DC activity. This correlation suggeststhat the sustained DC dysfunction initiated by life-threateninginflammation may contribute to the subsequent immunoparalysis,potentially as a result of the long-term maintenance of an abnormalgene expression pattern. In this review, we summarized the presentinformation regarding altered DC function after a severe, acuteinflammatory response and propose a mechanism, whereby epigeneticchanges can influence long-term gene expression patterns byDC, thus supporting an immunosuppression phenotype.

Key Words: sepsis • cytokine • Toll-like receptors • host defense • cell memory • long-term