IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

Stephen-Victor, Emmanuel; Sharma, Varun; Das, Mrinmoy; Karnam, Anupama; Saha, Chaitrali; Lecerf, Maxime; Galeotti, Caroline; Kaveri, Srini V.; Bayry, Jagadeesh

doi:10.3389/fimmu.2016.00465

Cited by 18 publications

(17 citation statements)

References 74 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, lentiviral transduction and LPS activation associated expression of secreted factors and cell surface molecules by ligand overexpressing DCs could contribute to modulation of T cell properties differently than that by APC subsets that naturally express elevated levels of these ligands. This is evident from our observation, in contrary to previous reports21,[49][50][51][52][53][54] , PD-L1 overexpressing engineered DCs do not induce an increase in Foxp3+ T cells, but these DCs suppress both Th1 and Th17 (IFNγ and IL17) responses. Nevertheless, the overall impact of engineered mono-and multi-ligand DCs on T cell function, as anticipated with enhanced engagement of T cell repressor receptors, is hyporesponsiveness/tolerance.…”

contrasting

confidence: 99%

Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance

Gudi

Karumuthil‐Melethil

Pérez

et al. 2019

Preprint

View full text Add to dashboard Cite

Inhibitory/repressor-receptors are upregulated significantly on activated T cells, and have been the molecules of attention as targets for inducing immune tolerance. Induction of effective antigen specific tolerance depends on concurrent engagement of the TCR and one or more of these inhibitory receptors. Here, we show, for the first time that dendritic cells (DCs) can be efficiently engineered to express multiple T cell inhibitory ligands, and enhanced engagement of T cell inhibitory receptors, upon antigen presentation, by these DCs can induce effective CD4+ T cell tolerance and suppress autoimmunity. Compared to control DCs, antigen presentation by DCs that ectopically express CTLA4, PD1 and BTLA selective ligands (B7.1wa, PD-L1, and HVEM-CRD1 respectively) individually (mono-ligand DCs) or in combination (multi-ligand DCs) causes an inhibition of CD4+ T cell proliferation and pro-inflammatory cytokine response, as well as increase in Foxp3+ Treg frequency and immune regulatory cytokine production.Administration of self-antigen (mouse thyroglobulin; mTg) loaded multi-ligand DCs caused hyporesponsiveness to mTg challenge, suppression of autoantibody production, and amelioration of experimental autoimmune thyroiditis. Overall, this study shows that engineered DC-directed enhanced concurrent activation of multiple T cell coinhibitory pathways is an effective way to induce self-antigen specific T cell tolerance to suppress ongoing autoimmunity.

show abstract

contrasting

confidence: 99%

Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance

Gudi

Karumuthil‐Melethil

Pérez

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Interleukin-1β IL-1β is part of an 11-member IL-1 cytokine family and signals through IL-1R. 88 IL-1β is mainly produced by monocytes and DCs and is vital to the Th17 response to Mtb. 88 IL-1β functions as the innate Th17-polarizing cytokine and determines the outcome of the Th17 response to Mtb and its antigen fractions.…”

Section: Figurementioning

confidence: 99%

“…88 IL-1β is mainly produced by monocytes and DCs and is vital to the Th17 response to Mtb. 88 IL-1β functions as the innate Th17-polarizing cytokine and determines the outcome of the Th17 response to Mtb and its antigen fractions. 89 The amounts of secreted IL-1β are significantly correlated with Th17 responses, 90 and exogenous replenishment of IL-1β is sufficient to markedly increase the Th17 response by the Mtb cytoplasmic fraction.…”

Section: Figurementioning

confidence: 99%

The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection

2017

View full text Add to dashboard Cite

Interleukin-17 (IL-17), IL-21, IL-22 and IL-23 can be grouped as T helper 17 (Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development. Here, we review Th17-related cytokines/Th17-like cells, networks/signals and their roles in immune responses or immunity against Mycobacterium tuberculosis (Mtb) infection. Published studies suggest that Th17-related cytokine pathways may be manipulated by Mtb microorganisms for their survival benefits in primary tuberculosis (TB). In addition, there is evidence that immune responses of the signal transducer and activator of transcription 3 (STAT3) signal pathway and Th17-like T-cell subsets are dysregulated or destroyed in patients with TB. Furthermore, Mtb infection can impact upstream cytokines in the STAT3 pathway of Th17-like responses. Based on these findings, we discuss the need for future studies and the rationale for targeting Th17-related cytokines/signals as a potential adjunctive treatment.

show abstract

“…With regard to the role of IL-1β and IL-23 in human TB, IL-1β is essential for the expansion of both IFN-γ − IL-17 + Th17 cells and IFN-γ + IL-17 + Th17 cells (311, 312). IL-23 promotes the development of IFN-γ + IL-17 + Th17 cells but promotes IFN-γ − IL-17 + Th17 cells if TGF-β is concomitantly present (312).…”

Section: Interactions Between T1-ifns and Th17 Immunity In Tbmentioning

confidence: 99%

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

et al. 2017

View full text Add to dashboard Cite

The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research.

show abstract

IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

Cited by 18 publications

References 74 publications

Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance

Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance

The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

Contact Info

Product

Resources

About