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CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity.

Signaling through IL-2/IL-15Rβ (CD122) is essential for the differentiation and function of T cells and NK cells. A mAb against CD122 has been implicated to suppress autoimmune type 1 diabetes (T1D) development in animal models. However, the mechanisms remain poorly understood. We find that in vivo administration of an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets. In contrast, islet CD4+Foxp3+ Tregs are only mildly affected. Second, CD122 blockade suppresses IFN-γ production in islet immune cells. Third, CD122 blockade inhibits the conversion of islet Th17 cells into diabetogenic Th1 cells. Furthermore, a combination of anti-CD122 mAb and Treg-trophic cytokines (IL-2 or IL-33) enhances the abundance and function of islet Tregs. In summary, these data provide crucial mechanistic insights into CD122 blockade-mediated immunoregulation and support therapeutic benefits of this combinational treatment in T1D.

How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance.

Background: There is mounting evidence for the health benefits of aromatic scents for the older people with dementia. However, existing research has focused on indoor aromatherapy using essential oils. It is necessary to explore the health benefits of smellscapes in the outdoor environment for older people with dementia. Aims and Objectives: This scoping review aims to examine existing evidence for smellscape as a healing factor in institutional garden for older people with dementia, try to bridge the knowledge gaps between outdoor sensory garden scents and aromatherapy to develop green care techniques that incorporate outdoor activities. Methods: Seven databases (Scopus, PubMed, PsycINFO, CINAHL, MEDLINE, Embase and Web of Science) were searched with English language articles published between 1990 and 2022. The PRISMA‐ScR Checklist was used. Results: Out of 1013 articles, 11 meet the inclusion criteria. The comprehensive health outcomes include five aspects: mental health; physical health; reduced agitation behaviour; improved cognitive function; and well‐being. These aspects are part of the rehabilitation model comprising the person (older people with dementia), environment (garden smellscapes) and outdoor activities (active or passive interventions or a combination). Conclusions: The smellscape, as a healing factor in the garden, not only benefits from evidence on indoor aromatherapy but also creates a sensory environment for older people with dementia by compensating for functional impairment, activity support and environmental creation, thereby promoting enhanced health and well‐being. Relevance to Clinical Practice: The research on the healing effects of smellscapes presented in this review offers a novel environmental intervention technique for transferring evidence on essential oils to outdoor sensory gardens. This green care technique is suggested to assist in the creation of healing environments and interventions for people with dementia who cannot be cured. No Patient or Public Contribution: This scoping review did not directly involve patient or public contributions to the manuscript. [ABSTRACT FROM AUTHOR]