Blockade of OSMRβ signaling ameliorates skin lesions in a mouse model of human atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Although IL-31, a type 2 helper T (Th2)-derived cytokine, is important to the development of pruritus and skin lesions in AD, the blockade of IL-31 signaling does not improve the skin lesions in AD. Oncostatin M (OSM), a member of IL-6 family of cytokines, plays important roles in the regulation of various inflammatory responses through OSM receptor β subunit (OSMRβ), a common receptor subunit for OSM and IL-31.

PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are the professional interferon (IFN)-producing cells of the immune system. pDCs specifically express Toll-like receptor (TLR)7 and TLR9 molecules and produce massive amounts of type I IFN by sensing microbial nucleic acids via TLR7 and TLR9. Here we report that protein kinase C and casein kinase substrate in neurons (PACSIN) 1, is specifically expressed in human and mouse pDCs.

Oncostatin M deficiency leads to thymic hypoplasia, accumulation of apoptotic thymocytes and glomerulonephritis.

Oncostatin M (OSM) has been implicated in immune regulation, though its precise role remains elusive. Here we show that OSM plays a crucial role in the prevention of autoimmune diseases. OSM-deficient mice showed normal development of T cells, B cells and DC; however, their thymus showed hypoplasia and altered medullary structure.

E-box protein E2-2 is a crucial regulator of plasmacytoid DC development.

DC play central roles in priming both innate and adaptive immune responses. Multiple DC subsets have been identified on the basis of their phenotype and function. Plasmacytoid DC (pDC) are professional IFN-producing cells that play an essential role in anti-viral immunity.

The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8.

The development of distinct dendritic cell (DC) subsets is regulated by cytokines. The ligand for the FMS-like tyrosine kinase 3 receptor (Flt3L) is necessary for plasmacytoid DC (pDC) and conventional DC (cDC) maturation. The cytokine GM-CSF inhibits Flt3L-driven pDC production while promoting cDC growth.

A critical role of costimulation during intrathymic development of invariant NK T cells.

CD1d-restricted Valpha14(+) invariant NK T (iNKT) cells are a specialized alphabeta T cell subset that regulates both innate and adaptive immunity. Although costimulatory molecules are required for the activation of conventional T cells and for the development of Foxp3(+) T cells, their role in iNKT cell regulation is unclear. Here we report that mice deficient in CD80/CD86 and/or B7h exhibit severe defects in thymic iNKT cell maturation, associated with largely reduced iNKT cell number in the thymus and the periphery.

IL-18 produced by thymic epithelial cells induces development of dendritic cells with CD11b in the fetal thymus.

Thymic dendritic cells (DCs) are suggested to be involved in T cell selection; however, their exact origin and function remain to be established. Although DCs in the adult thymus are mostly CD8alpha(+)CD11b(-), we found that CD8alpha(-)CD11b(+) DCs were abundantly present in the fetal thymus and they possessed antigen-presenting activity. Interestingly, these CD11b(+) DCs were significantly decreased in mice deficient for TNFR-associated factor 6 (TRAF6), a key signaling molecule downstream of IL-1 and tumor necrosis factor-alpha that have been known to induce DCs from intra-thymic precursor cells.

Development of CD4+ macrophages from intrathymic T cell progenitors is induced by thymic epithelial cells.

It was recently demonstrated that there are CD4(+) macrophages, which exhibit strong phagocytic activity, in the thymus. They are suggested to play an important role for the elimination of apoptotic thymocytes. However, the origin and nature of CD4(+) macrophages in the thymus remain unexplored.

Cutting Edge: A possible role for CD4+ thymic macrophages as professional scavengers of apoptotic thymocytes.

A vast majority of thymocytes are eliminated during T cell development by apoptosis. However, apoptotic thymocytes are not usually found in the thymus, indicating that apoptotic thymocytes must be eliminated rapidly by scavengers. Although macrophages and dendritic cells are believed to play such role, little is known about scavengers in the thymus.