IL-17A and Th17 Cells in Lung Inflammation: An Update on the Role of Th17 Cell Differentiation and IL-17R Signaling in Host Defense against Infection

Tsai, Hsing-Chuan; Velichko, Sharlene; Hung, Li-Yin; Wu, Reen

doi:10.1155/2013/267971

Cited by 90 publications

(91 citation statements)

References 182 publications

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“…However, a growing number of recent studies suggest that this response is also involved in the control of intracellular microorganisms, such as Listeria monocytogenes, Salmonella enterica, and Mycobacterium tuberculosis (reviewed in Refs. 62,63). In the lungs, IL-17A was reported to act primarily on nonhematopoietic cells, such as epithelial cells, endothelial cells, and fibroblasts (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

“…In the lungs, IL-17A was reported to act primarily on nonhematopoietic cells, such as epithelial cells, endothelial cells, and fibroblasts (reviewed in Ref. 63), to promote the production of numerous proteins with antimicrobial properties and chemokines that attract neutrophils. Although first identified in CD4 + T cells, IL-17A can also be produced by CD8 + T cells and innate cells, such as g/d + T cells, invariant NKT cells, neutrophils, and innate lymphoid cells (63).…”

Section: Discussionmentioning

confidence: 99%

“…63), to promote the production of numerous proteins with antimicrobial properties and chemokines that attract neutrophils. Although first identified in CD4 + T cells, IL-17A can also be produced by CD8 + T cells and innate cells, such as g/d + T cells, invariant NKT cells, neutrophils, and innate lymphoid cells (63). There have been few studies of the function of IL-17A-mediated responses in immunity to Brucella organisms.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Mambres

Machelart

Potemberg

et al. 2016

The Journal of Immunology

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The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis. Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35−/− mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35– and IL-17A–dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4+ and CD8+ α/β+ T cells are sufficient to mount a protective immune response and that an IL-17A–mediated response can compensate for the partial deficiency of an IFN-γ–mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ–and IL-17RA–mediated responses in the control of mucosal infection by Brucella.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Mambres

Machelart

Potemberg

et al. 2016

The Journal of Immunology

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“…IL-17 and IL-17F can form homo-or hetero-dimers that bind a heteromeric receptor complex containing IL-17RA and/or IL-17RC [2,23,24]. Binding of IL-17 to the IL-17 receptors typically leads to activation of the NF-κB, MAPKs, ERK, or C/EBPs signaling pathways [25].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Act1 was identified as an important mediator via its interaction with IL-17R through TRAF6-dependent and -independent downstream pathways [26]. In addition, IL-17-mediated activation of STAT3 has been reported in airway epithelial cells [27] and smooth muscle cells [23,28]. However, the requirement of STAT3 in IL-17-activated endothelial cells has not been fully explored.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Yuan

Zhang

Zhuang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. Methods: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. Results: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-α, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-α, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. Conclusions: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment.

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Immune Checkpoint Ligand Bioengineered Schwann Cells as Antigen‐Specific Therapy for Experimental Autoimmune Encephalomyelitis

Tisch

Wang

2021

Advanced Materials

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disorder multiple sclerosis (MS), which disrupts communication between the brain and peripheral system. [4,6] At least 2.5 million people worldwide are affected by MS. Most patients initially experience episodes of reversible neurological deficits, followed by remission, before chronic neurological deterioration leads to severe, irreversible disabilities. [6] Unfortunately, MS cannot be completely cured, although available immunomodulatory therapies reduce the frequency and severity of MS relapses by inducing antigen-specific immunotolerance, [7] thus delaying the accumulation of disabilities. New treatment strategies involve the induction of antigen-specific T reg cells [8,9] that suppress inflammatory pathogens and restore peripheral immunotolerance without causing systemic immunosuppression.Immune checkpoints play key roles in maintaining immunotolerance. [10] For example, studies have found that coinhibitory immune checkpoint pathways such as programmed death 1 (PD-1)-PD ligand 1 (PD-L1), [10,11] and cytotoxic T lymphocyte associated protein 4 (CTLA-4)-cluster of differentiation 86 (CD86) [10,12] directly regulate the development and maintenance of myelin-specific induced T reg cells. [13] Here, we aimed to determine whether the intravenous (i.v.) administration of coinhibitory immune checkpoint ligand-bioengineered glia can be used as a prophylactic treatment to prevent the development of MS or use in therapeutic Failure to establish immune tolerance leads to the development of autoimmune disease. The ability to regulate autoreactive T cells without inducing systemic immunosuppression represents a major challenge in the development of new strategies to treat autoimmune disease. Here, a translational method for bioengineering programmed death-ligand 1 (PD-L1)-and cluster of differentiation 86 (CD86)-functionalized mouse Schwann cells (SCs) to prevent and ameliorate multiple sclerosis (MS) in established mouse models of chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE) is described. It is shown that the intravenous (i.v.) administration of immune checkpoint ligand functionalized mouse SCs modifies the course of disease and ameliorates EAE. Further, it is found that such bioengineered mouse SCs inhibit the differentiation of myelin-specific helper T cells into pathogenic T helper type-1 (T h 1) and type-17 (T h 17) cells, promote the development of tolerogenic myelin-specific regulatory T (T reg ) cells, and resolve inflammatory central nervous system microenvironments without inducing systemic immunosuppression.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202107392.

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IL-17A and Th17 Cells in Lung Inflammation: An Update on the Role of Th17 Cell Differentiation and IL-17R Signaling in Host Defense against Infection

Cited by 90 publications

References 182 publications

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Immune Checkpoint Ligand Bioengineered Schwann Cells as Antigen‐Specific Therapy for Experimental Autoimmune Encephalomyelitis

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