FcεRI Signaling in the Modulation of Allergic Response: Role of Mast Cell-Derived Exosomes.

Mast cells (MCs) are immune cells that act as environment resident sentinels playing a crucial role in Th2-mediated immune responses, including allergic reactions. Distinguishing features of MCs are the presence of numerous cytoplasmic granules that encapsulate a wide array of preformed bio-active molecules and the constitutive expression of the high affinity receptor of IgE (FcεRI). Upon FcεRI engagement by means of IgE and multivalent antigens, aggregated receptors trigger biochemical pathways that ultimately lead to the release of granule-stored and newly synthesized pro-inflammatory mediators. Additionally, MCs are also able to release exosomes either constitutively or upon stimulation. Exosomes are nanosized vesicles of endocytic origin endowed with important immunoregulatory properties, and represent an additional way of intercellular communication. Interestingly, exosomes generated upon FcεRI engagement contain co-stimulatory and adhesion molecules, lipid mediators, and MC-specific proteases, as well as receptor subunits together with IgE and antigens. These findings support the notion that FcεRI signaling plays an important role in influencing the composition and functions of exosomes derived by MCs depending on their activation status.

Immunoregulatory Property of C-Type Lectin-Like Receptors in Fibrosing Interstitial Lung Diseases.

The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibrosis has implicated immunoreceptor tyrosine-based motif-bearing CTLRs as being involved, either directly or indirectly, in the pathogenesis of fibrosing ILD.

The significance of immunoregulatory receptor TIGIT expression in thymus and peripheral blood mononuclear cells in an “anger” rat model / 中国组织工程研究

BACKGROUND: Previous studies have shown that stress response can cause immune dysfunction in the body. T cell immunoglobulin and ITIM domain (TIGIT) is an immunoregulatory receptor that can inhibit T cell activity, promote T cell apoptosis and promote T cell subgroup distribution imbalance. Whether the immune response mechanism of stress response is related to the expression and function of TIGIT is still unclear. OJECTIVE: To investigate the expression of immunomodulatory receptor TIGIT in thymus cells and peripheral blood mononuclear cells in an anger rat model and its significance to immune function. METHODS: Forty-eight Wistar male rats were randomly divided into normal group, 7-, 14-and 21-day model groups, with 12 rats in each group. In addition to the blank group, social isolation method with plantar electric shock method was used to establish rat anger models in the other groups. The behavioral changes of rats were observed by open-field test and aggressive behavior test, and the changes in body mass and thymus index before and after the test were recorded. The positive expression of TIGIT in thymus and peripheral blood mononuclear cells of rats in each group was observed by immunohistochemistry, and the expression levels of CD4+ and CD8+ T cells in the peripheral blood were measured by flow cytometry. The correlation between TIGIT expression in thymus and peripheral blood mononuclear cells and the CD4+/CD8+ ratio of T cell subsets in the peripheral blood was analyzed. An ethical approval for the study was obtained from the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine. RESULTS AND CONCLUSION: In the 14-and 21-day model groups, the scores of horizontal and vertical activities in the open-field test of rats were higher than the control group (P < 0.05 or P < 0.01). In the 7-, 14-and 21-day model groups, the attack hiding time of the attack behavior test was significantly shortened (P < 0.01), the number of attacks and the cumulative attack time were significantly increased (P < 0.01), and the body mass and thymus index were significantly decreased compared with the control group (P < 0.05 or P < 0.01). In the 7-and 14-day model groups, the expression level of TIGIT in thymus and peripheral blood mononuclear cells was significantly higher than the control group (P < 0.01), while the CD4+/CD8+ ratio level of the peripheral blood T cell subsets was significantly lower than the control group (P < 0.05 or P < 0.01). The CD4+/CD8+ ratio of T cell subsets in the peripheral blood of random samples of rats was negatively correlated with the expression level of TIGIT in T cells of thymus (r2=0.627 0, P < 0.000 1) and in mononuclear cells (r2=0.624 4, P < 0.000 1). These results indicate that the model rats in the stress-induced anger state have obvious changes in animal behavior, present with thymus atrophy and abnormalities in peripheral blood T lymphocyte subsets CD4+/CD8+ ratio and immune function. This phenomenon may be related to the thymus and peripheral blood mononuclear cells TIGIT expression level, but the specific mechanism needs to be elucidated further.

Chicken immunoregulatory Ig-like receptor families: an overview and expression details on ggTREM-A1.

Paired immunoregulatory receptors facilitate the coordination of the immune response at the cellular level. In recent years, our group characterized chicken homologues to mammalian immunoregulatory Ig-like receptor families. The first part of this review focuses on the current progress on chicken immunoregulatory Ig-like receptor families. One of these receptors is gallus gallus TREM-A1, which was described as the only member of the chicken TREM family with activating potential. The second part of this review presents a study initiated to further characterize ggTREM-A1 expression. For this purpose we established real-time RT-PCR and generated a specific mab to analyze the expression profile of ggTREM-A1 on mRNA and protein level, respectively. GgTREM-A1 mRNA was predominantly expressed in macrophages, but was also detected in brain, bone marrow, bursa, thymus, spleen and PBMC. Analyzing ggTREM-A1 surface expression by mab staining validated the expression on macrophages. Additionally, we showed high expression on blood monocytes, heterophils and NK cells and on monocytes isolated from bone marrow. Moreover, we detected ggTREM-A1 protein also on thrombocytes, B and T cell subsets, but antigen expression seemed to be lower and more variable in these cells. Immunohistochemistry of chicken brain tissue, combining ggTREM-A1 mab and various markers specific for various brain cell subsets showed expression of ggTREM-A1 on microglial cells, but also on neurons, astrocytes and oligodendrocytes. In conclusion, ggTREM-A1 is expressed on a variety of cells, relevant for the immune system, possibly combining physiological function of different mammalian TREM.