Signaling Through gp130 Compromises Suppressive Function in Human FOXP3 Regulatory T Cells.

The CD4FOXP3 regulatory T cell (Treg) subset is an indispensable mediator of immune tolerance. While high and stable expression of the transcription factor FOXP3 is considered a hallmark feature of Treg cells, our previous studies have demonstrated that the human FOXP3 subset is functionally heterogeneous, whereby a sizeable proportion of FOXP3 cells in healthy individuals have a diminished capacity to suppress the proliferation and cytokine production of responder cells. Notably, these non-suppressive cells are indistinguishable from suppressive Treg cells using conventional markers of human Treg.

Suppression by human FOXP3 regulatory T cells requires FOXP3-TIP60 interactions.

CD4FOXP3 regulatory T (T) cells are critical mediators of immune tolerance, and their deficiency owing to mutations in immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) patients results in severe autoimmunity. Different mutations result in a wide range of disease severity, reflecting the relative importance of the affected residues in the integrity of the FOXP3 protein and its various molecular interactions. We characterized the cellular and molecular impact of the most common IPEX mutation, p.

The immunological and genetic basis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.

Purpose Of Review: This article presents a comprehensive review of the immunodysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, covering both the clinical and molecular aspects of the disease. (Figure is included in full-text article.)

Recent Findings: The IPEX syndrome is a rare immunological disorder in humans caused by inheritable mutations in the FOXP3 gene, the master transcriptional regulator for the development and function of CD4 regulatory T (Treg) cells.

Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T cells.

Two distinct subsets of CD4(+)Foxp3(+) regulatory T (Treg) cells have been described based on the differential expression of Helios, a transcription factor of the Ikaros family. Efforts to understand the origin and biological roles of these Treg populations in regulating immune responses have, however, been hindered by the lack of reliable surface markers to distinguish and isolate them for subsequent functional studies. Using a single-cell cloning strategy coupled with microarray analysis of different Treg functional subsets in humans, we identify the mRNA and protein expression of TIGIT and FCRL3 as a novel surface marker combination that distinguishes Helios(+)FOXP3(+) from Helios(-)FOXP3(+) memory cells.

Functional dynamics of Foxp3⁺ regulatory T cells in mice and humans.

Forkhead box protein 3 (Foxp3)(+) regulatory T (Treg) cells are critical mediators for the establishment of self-tolerance and immune homeostasis and for the control of pathology in various inflammatory responses. While Foxp3(+) Treg cells often control immune responses in secondary lymphoid tissues, they must also traffic to and persist within non-lymphoid tissues, where they integrate various environmental cues to coordinate and adapt their effector acitvities in these sites. In recent years, our group has made use of several mouse models, including the non-obese diabetic model of type 1 diabetes, to characterize the factors, which impact the homeostasis, function, and reprogramming potential of Foxp3(+) Treg cells in situ.

Altered T helper 17 responses in children with food allergy.

Background: While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed.

Methods: Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study.

The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome is a rare disorder in humans caused by germ-line mutations in the FOXP3 gene, a master transcriptional regulator for the development of CD4 regulatory T (Treg) cells. This T cell subset has global inhibitory functions that maintain immune homeostasis and mediate self-tolerance. Treg developmental deficiency or dysfunction is a hallmark of IPEX.

Acquired Omenn-like syndrome, a novel posttransplant autoaggression syndrome reversed by rapamycin.

Graft-versus-host disease is uncommon in autologous hematopoietic cell transplantation (HCT) and is typically brief and mild. We report unusual, protracted, and severe Omenn syndrome-like autoaggression following autologous HCT. We identified a profound FOXP3(+) regulatory T cell defect that coincided with hyperinflammatory T cell responses which were reversible with rapamycin in vitro.