Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation.

Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell- and B cell-sufficient mice, remains largely unclear.

Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability.

Whether interleukin-17A (IL-17A) has pathogenic and/or protective roles in the gut mucosa is controversial and few studies have analyzed specific cell populations for protective functions within the inflamed colonic tissue. Here we have provided evidence for IL-17A-dependent regulation of the tight junction protein occludin during epithelial injury that limits excessive permeability and maintains barrier integrity. Analysis of epithelial cells showed that in the absence of signaling via the IL-17 receptor adaptor protein Act-1, the protective effect of IL-17A was abrogated and inflammation was enhanced.

Melatonin Lulling Th17 Cells to Sleep.

In this issue, Farez et al. report that the circadian hormone melatonin, whose levels vary with seasonal changes in night length, shifts the immune response toward an anti-inflammatory state that may explain the seasonal variability of multiple sclerosis disease activity.

A Highly Focused Antigen Receptor Repertoire Characterizes γδ T Cells That are Poised to Make IL-17 Rapidly in Naive Animals.

Interleukin (IL)-17 plays a key role in immunity. In acute infections, a rapid IL-17 response must be induced without prior antigen exposure, and γδ T cells are the major initial IL-17 producers. In fact, some γδ T cells make IL-17 within hours after an immune challenge.

Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets.

The recognized diversity of innate lymphoid cells (ILCs) is rapidly expanding. Three ILC classes have emerged, ILC1, ILC2 and ILC3, with ILC1 and ILC3 including several subsets. The classification of some subsets is unclear, and it remains controversial whether natural killer (NK) cells and ILC1 cells are distinct cell types.

The emerging landscape of RORγt biology.

The transcription factor retinoid-related orphan receptor gamma t (RORγt) has emerged as an exciting target for inflammatory diseases. Xiao et al. (2014) show that a new class of RORγt antagonists can inhibit the inflammatory function of T helper 17 cells without altering RORγt occupancy on its target genes.

Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens.

Defense against attaching-and-effacing bacteria requires the sequential generation of interleukin 23 (IL-23) and IL-22 to induce protective mucosal responses. Although CD4(+) and NKp46(+) innate lymphoid cells (ILCs) are the critical source of IL-22 during infection, the precise source of IL-23 is unclear. We used genetic techniques to deplete mice of specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the attaching-and-effacing pathogen Citrobacter rodentium.

Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells.

Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced interferon-γ (IFN-γ) in response to IL-12 and IL-15 and had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting, and a memory-activated phenotype.

AHR and the Transcriptional Regulation of Type-17/22 ILC.

Mucosal innate lymphoid cells (ILCs) are an emerging population of diverse and heterogeneous immune cells, all with the unique ability to mount a rapid response against invading pathogens. They are further divided into subsets based on their differing cell surface markers as well as in their functional specialization. In this review, we summarize recent reports describing the importance of the transcription factor aryl hydrocarbon receptor (AHR) in regulating the development of one of these subsets, the Type-17/22 ILCs, as well as in the organization of postnatal lymphoid structures.

AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.

Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection.

Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma.

Object: In this paper the authors describe the indications for and the results and complications of repeated transsphenoidal surgery (RTSS) to treat recurrent or residual pituitary adenoma.

Methods: A retrospective review was conducted of 96 consecutive patients who underwent RTSS to treat recurrent or residual pituitary adenoma. Ninety-six patients underwent RTSS: 42 to treat a recurrent or residual pituitary mass and 54 to treat a recurrent or persistent hormone hypersecretion.

Surgery for Rathke cleft cysts: technical considerations and outcomes.

Object: The aim of this study was to identify the optimal surgical goals and techniques for managing symptomatic Rathke cleft cysts (RCCs).

Methods: The authors conducted a retrospective study of 62 consecutive patients who had undergone surgery for RCCs. Postoperative follow up was a mean of 28 months.

MR cholangiography in the evaluation of neonatal cholestasis: initial results.

Purpose: To retrospectively analyze prospective magnetic resonance (MR) cholangiographic interpretations of findings and compare them with clinical outcome and to determine the accuracy of MR cholangiography in depicting extrahepatic biliary atresia and helping to distinguish it from other causes of neonatal jaundice.

Materials And Methods: Twenty-six infants (15 male, 11 female; median age, 2 months) underwent MR cholangiography with a 1.5-T MR imaging unit.