Volume 14 Issue 10, October 2013

The skin is a highly complex organ and the main body barrier against pathogens and other environmental factors. Heath and Carbone outline many of the innate and adaptive immune cell types associated with the skin.

Macrophages populate tissues under homeostatic conditions. Taylor and colleagues discuss the heterogeneity of tissue macrophage populations, and how they contribute to tissue function and immune surveillance.

The liver is important in mediating immunity to blood-borne infections. Jenne and Kubes review the liver as an immune organ and discuss the roles of liver-resident cells and their interactions with circulating immune cells.

Regulatory T (T_reg) cells modulate immune cell responses. Mathis and colleagues review the specialized roles played by tissue-specific Treg cells and reveal new functions that can be attributed to distinct T_reg cell subsets.

Tumors can evade immune system–mediated destruction despite expressing antigenic neoepitopes. Gajewski, Schreiber and Fu discuss how the tumor microenvironment harnesses innate and adaptive immune cell regulatory processes to promote tumor survival.

Signaling via the interleukin 1 (IL-1) family, particularly by IL-1β, has long been linked to the pathogenesis of atherosclerosis. Findings that atherogenic fatty acids induce IL-1α to promote vascular inflammation identify a key role for this less-well-studied cytokine.

The transcription factor GATA-3 is expressed in quiescent hematopoietic stem cells (HSCs) with long-term repopulating ability. Stress-mediated activation of HSCs promotes localization of GATA-3 to the nucleus in a manner dependent on the mitogen-activated protein kinase p38α and restricts self-renewal.

Zinc fingers 1 and 4 of Ikaros have unique functions in the selection of Ikaros target genes, lymphocyte development and the suppression of leukemogenesis.

Although GATA-3 is expressed in hematopoietic stem cells, its function there remains unclear. Iscove and colleagues show that GATA-3 inhibits the self-renewal potential of long-term hematopoietic stem cells downstream of p38 signaling.

Chronic inflammation is a fundamental aspect of metabolic disorders such as atherosclerosis. Freigang and colleagues report that fatty acids are potent inducers of IL-1α, which drives vascular inflammation.

The immunoregulatory effect of IL-27 is thought to act mainly on T cells. Quintana and colleagues show that IL-27 also converts conventional DCs into immunosuppressive cells.

Effector memory CD8⁺ T cells are capable of rapid IFN-γ production. Hess and colleagues show that antigenic reactivation triggers enhanced glycolytic flux, which is required for early IFN-γ recall responses.

The transcription factor Ikaros, which is essential for lymphocyte development, contains multiple zinc fingers. Smale and colleagues show that mice lacking different zinc fingers develop distinct lymphocyte-developmental defects and tumor susceptibility.

Diffuse large B cell lymphomas can arise from dysregulation of BCL6 expression. Dalla-Favera and colleagues show that the transcription factor MEF2B regulates BCL6 and is commonly associated with the generation of such lymphomas.

Silva-Santos and colleagues use genome-wide characterization of the methylation patterns of histone H3 and analysis of transcription factor expression to identify the regulatory framework of peripheral interferon-γ-producing or interleukin 17–producing γδ T cell subsets.

Immune cells are found in diverse nonlymphoid tissues where they patrol against infection and injury and help to maintain homeostasis. This month's Focus features five specially commissioned Reviews that discuss interactions and functions of tissue-resident leukocytes.