Do insights from mice imply that combined Th2 and Th17 therapies would benefit select severe asthma patients?

Poynter, Matthew E.

doi:10.21037/atm.2016.11.79

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…Although IL-17 is most richly expressed by 17 cells, it can also be produced by other immune cells, including macrophages, B cells, natural killer T cells, innate lymphocytes, and CD8+T cells [54]. Indeed, IL-17 and 17 cells have been shown to be associated with human autoimmune diseases in many tissue regions, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma [55][56][57][58][59][60][61]. Recent evidence suggests that 17 cells are also associated with 2 hypersensitivity [62,63].…”

Section: And Il-7 May Promote Acmentioning

confidence: 99%

The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

Meng

Shi

Zhang

et al. 2020

Journal of Ophthalmology

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Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients’ quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.

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Section: And Il-7 May Promote Acmentioning

confidence: 99%

The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

Meng

Shi

Zhang

et al. 2020

Journal of Ophthalmology

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“…The authors propose that in asthma, a predisposition to T2 inflammation is driven towards T17-mediated inflammation by corticosteroid therapy [128]. This hypothesis would have important implications for patients receiving type 2-targeting biologics, although the study has provoked some controversy [129,130].…”

Section: Is There a Reciprocal Relationship Between T2 And T17 Inflammation?mentioning

confidence: 99%

“…There are as yet no prospective clinical data showing development of T17 inflammation in people receiving blockade of T2 pathways. Whether such an increase T17 inflammation would be harmful is also unknown [130], and will be important to investigate.…”

Section: Is There a Reciprocal Relationship Between T2 And T17 Inflammation?mentioning

confidence: 99%

The role of interleukin-17 in asthma: a protective response?

Hynes

Hinks

2020

ERJ Open Res

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While there now exist effective treatments for type 2 high, eosinophilic asthma, there are no specific therapies for 40–50% of people with asthma with other phenotypes, which result from poorly understood underlying pathological mechanisms. One such pathology is neutrophilic inflammation, which has been associated with interleukin (IL)-17 family cytokines. Human genetic studies identified IL-17 polymorphisms associated with asthma; in murine models of allergic airways disease, IL-17A contributes to airway hyperresponsiveness, and in humans, elevated airway IL-17A levels are repeatedly observed in severe asthma. However, the directionality of this association is unknown, and the assumption that IL-17 cytokines drive disease pathology remains speculative. Here, we explore the evidence underlying the relationship between IL-17 and asthma, we review lessons learned from investigating IL-17 in other inflammatory diseases, and discuss the possibility that IL-17 may even be protective in asthma rather than pathogenic. We also critically examine the newly proposed paradigm of a reciprocal relationship between type 2 and type 17 airways inflammation. In summary, we suggest an association between IL-17 and asthma, but research is needed examining the diverse functions of these cytokines, their longitudinal stability, their response to clinical interventions, and for mechanistic studies determining whether they are protective or pathogenic.

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“…In addition, granulocyte colony-stimulating factor and GM-CS, but not IL-17A, levels were increased in patients with T H 2/T H 17-low asthma, raising the possibility that these cytokines might also be inhibited by IL-4 or some other factor produced by T H 2 cells. Early clinical studies blocking IL-4 and/or IL-13 signaling have not yet been noted to result in a neutrophilic airway phenotype 10 ; however, the possibility that T H 2 cytokines might inhibit neutrophil recruitment is plausible based on the studies described above, and there needs to be vigilance that such phenotypes do not develop with the use of pharmacologic agents that antagonize the IL-4/IL-13 production or signaling axis. Although there is associative evidence that IL-17 might be involved in asthma pathogenesis, inhibition of IL-17 signaling with an IL-17 receptor antagonist did not improve asthma outcomes, 11 therefore pinpointing a biomarker that identifies who might have T H 17driven asthma pathogenesis is critical to determine the patient population those would benefit from either a more potent IL-17 antagonist or dual T H 2/T H 17 antagonism.…”

mentioning

confidence: 99%

Is IL-1β inhibition the next therapeutic target in asthma?

Peebles

2017

Journal of Allergy and Clinical Immunology

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Do insights from mice imply that combined Th2 and Th17 therapies would benefit select severe asthma patients?

Cited by 4 publications

References 19 publications

The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

The role of interleukin-17 in asthma: a protective response?

Is IL-1β inhibition the next therapeutic target in asthma?

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