scholarly journals The Role of Co-Signaling Molecules in Psoriasis and Their Implications for Targeted Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Suqing Liu ◽  
Jinhua Xu ◽  
Jinfeng Wu
Keyword(s):  
T Cells ◽  
Signaling Molecules ◽  
Pathological Process ◽  
T Cell Response ◽  
Significant Progress ◽  
Broad Application ◽  
Immune Mediated ◽  
Inhibitory Molecules ◽  
Application Prospects

Psoriasis is a chronic, systemic immune-mediated inflammatory disease manifesting in the skin, joint or both. Co-signaling molecules are essential for determining the magnitude of the T cell response to the antigen. According to the function of co-signaling molecules, they can be divided into co-stimulatory molecules and co-inhibitory molecules. The role of co-signaling molecules in psoriasis is recognized, mainly including the co-stimulatory molecules CD28, CD40, OX40, CD27, DR3, LFA-1, and LFA-3 and the co-inhibitory molecules CTLA-4, PD-1, and TIM-3. They impact the pathological process of psoriasis by modulating the immune strength of T cells, regulating the production of cytokines or the differentiation of Tregs. In recent years, immunotherapies targeting co-signaling molecules have made significant progress and shown broad application prospects in psoriasis. This review aims to outline the possible role of co-signaling molecules in the pathogenesis of psoriasis and their potential application for the treatment of psoriasis.

scholarly journals Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Load ◽  
Peritoneal Macrophages ◽  
T Cell Response ◽  
No Production ◽  
Similar Reduction ◽  
Ifn Γ

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.

scholarly journals Functional heterogeneity of CD4+ T cells in liver inflammation

2021 ◽  
Author(s):  
Franziska Muscate ◽  
Anna Woestemeier ◽  
Nicola Gagliani
Keyword(s):  
T Cells ◽  
Essential Role ◽  
Inflammatory Diseases ◽  
Cell Polarization ◽  
Maturation Stage ◽  
Liver Inflammation ◽  
Functional Heterogeneity ◽  
Immune Mediated ◽  
T Cell Polarization

AbstractCD4+ T cells play an essential role in orchestrating adequate immunity, but their overactivity has been associated with the development of immune-mediated inflammatory diseases, including liver inflammatory diseases. These cells can be subclassified according to their maturation stage, cytokine profile, and pro or anti-inflammatory functions, i.e., functional heterogeneity. In this review, we summarize what has been discovered so far regarding the role of the different CD4+ T cell polarization states in the progression of two prominent and still different liver inflammatory diseases: non-alcoholic steatohepatitis (NASH) and autoimmune hepatitis (AIH). Finally, the potential of CD4+ T cells as a therapeutic target in both NASH and AIH is discussed.

scholarly journals The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Yong Tang ◽  
Marie J. Desierto ◽  
Jichun Chen ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transcription Factor ◽  
Transforming Growth Factor ◽  
Bone Marrow Failure ◽  
Critical Role ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Immune Mediated

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

scholarly journals Antioxidant Treatment Reduces Expansion and Contraction of Antigen-Specific CD8+ T Cells during Primary but Not Secondary Viral Infection

2004 ◽  
Vol 78 (20) ◽  
pp. 11246-11257 ◽  
Author(s):  
Nathan G. Laniewski ◽  
Jason M. Grayson
Keyword(s):  
T Cells ◽  
Viral Infection ◽  
Large Scale ◽  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Response ◽  
Oxygen Intermediates ◽  
Mimetic Compound

ABSTRACT During many viral infections, antigen-specific CD8+ T cells undergo large-scale expansion. After viral clearance, the vast majority of effector CD8+ T cells undergo apoptosis. Previous studies have implicated reactive oxygen intermediates (ROI) in lymphocyte apoptosis. The purpose of the experiments presented here was to determine the role of ROI in the expansion and contraction of CD8+ T cells in vivo during a physiological response such as viral infection. Mice were infected with lymphocytic choriomeningitis virus (LCMV) and treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a metalloporphyrin-mimetic compound with superoxide dismutase activity, from days 0 to 8 postinfection. At the peak of CD8+-T-cell response, on day 8 postinfection, the numbers of antigen-specific cells were 10-fold lower in MnTBAP-treated mice than in control mice. From days 8 to 30, a contraction phase ensued where the numbers of antigen-specific CD8+ T cells declined 25-fold in vehicle-treated mice compared to a 3.5-fold decrease in MnTBAP-treated mice. Differences in contraction appeared to be due to greater proliferation in drug-treated mice. By day 38, the numbers of antigen-specific CD8+ memory T cells were equivalent for the two groups. The administration of MnTBAP during secondary viral infection had no effect on the expansion of antigen-specific CD8+ secondary effector T cells. These data suggest that ROI production is critical for the massive expansion and contraction of antigen-specific CD8+ T cells during primary, but not secondary, viral infection.

Shaping the CD4+ memory immune response against tuberculosis: the role of antigen persistence, location and multi-functionality

2012 ◽  
Vol 3 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Lindsay Ancelet ◽  
Joanna Kirman
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Rational Design ◽  
Memory T Cells ◽  
T Cell Response ◽  
Intracellular Pathogens ◽  
Memory T Cell ◽  
Antigen Persistence ◽  
Memory Immune Response

AbstractEffective vaccination against intracellular pathogens, such as tuberculosis (TB), relies on the generation and maintenance of CD4 memory T cells. An incomplete understanding of the memory immune response has hindered the rational design of a new, more effective TB vaccine. This review discusses how the persistence of antigen, the location of memory cells, and their multifunctional ability shape the CD4 memory T cell response against TB.

scholarly journals MyD88 Intrinsically Regulates CD4 T-Cell Responses

2008 ◽  
Vol 83 (4) ◽  
pp. 1625-1634 ◽  
Author(s):  
Shenghua Zhou ◽  
Evelyn A. Kurt-Jones ◽  
Anna M. Cerny ◽  
Melvin Chan ◽  
Roderick Terry Bronson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
T Cell Response ◽  
Microbial Pathogens ◽  
Wasting Disease ◽  
Lcmv Infection

ABSTRACT Myeloid differentiation factor 88 (MyD88) is an essential adaptor protein in the Toll-like receptor-mediated innate signaling pathway, as well as in interleukin-1 receptor (IL-1R) and IL-18R signaling. The importance of MyD88 in the regulation of innate immunity to microbial pathogens has been well demonstrated. However, its role in regulating acquired immunity to viral pathogens and neuropathogenesis is not entirely clear. In the present study, we examine the role of MyD88 in the CD4+ T-cell response following lymphocytic choriomeningitis virus (LCMV) infection. We demonstrate that wild-type (WT) mice developed a CD4+ T-cell-mediated wasting disease after intracranial infection with LCMV. In contrast, MyD88 knockout (KO) mice did not develop wasting disease in response to the same infection. This effect was not the result of MyD88 regulation of IL-1 or IL-18 responses since IL-1R1 KO and IL-18R KO mice were not protected from weight loss. In the absence of MyD88, naïve CD4+ T cells failed to differentiate to LCMV-specific CD4 T cells. We demonstrated that MyD88 KO antigen-presenting cells are capable of activating WT CD4+ T cells. Importantly, when MyD88 KO CD4+ T cells were reconstituted with an MyD88-expressing lentivirus, the rescued CD4+ T cells were able to respond to LCMV infection and support IgG2a antibody production. Overall, these studies reveal a previously unknown role of MyD88-dependent signaling in CD4+ T cells in the regulation of the virus-specific CD4+ T-cell response and in viral infection-induced immunopathology in the central nervous system.

Sign in / Sign up

Export Citation Format

Share Document