The role of type 2 innate lymphoid cells in eosinophilic asthma

Abstract

Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4 + T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4 + T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to "initiate" eosinophilic responses, whereas CD4 + T cells act locally and systemically to "perpetuate" eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5 + IL-13 + ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases. K E Y W O R D Seosinophilic asthma, eosinophilopoiesis, innate lymphoid cells NMU, neuromedin U; NMUR, neuromedin U receptor; PC 20 , concentration required to achieve a 20% decrease in FEV 1 ; PLZF, pro-myelocytic leukemia zinc finger; TOX, thymocyte selection associated HMB boxprotein; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor. this review, we will discuss the role of innate lymphoid cells (ILCs) in eosinophilic asthma and the potential targets that drive persistent airway eosinophilia.

Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling

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Equine Asthma: Current Understanding and Future Directions

“…In recent years there has emerged another lymphoid cell that participates in host responses to mucosal injury. These innate lymphoid cells are lineage negative, lacking the usual lymphocyte surface markers (9). They express similar panels of cytokines to the T helper subsets and are labeled innate lymphoid cell (ILC) 1, 2, and 3.…”

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…Defining disease endotypes based on key pathogenetic mechanisms is the next logical step, and both type 2 and non‐type 2 asthma endotypes have been postulated 23 . Type 2 endotype is initiated either directly via thymic stromal lymphopoietin (TSLP), IL‐25 and IL‐33 released by bronchial epithelial cells, or indirectly via the stimulation of Th2 cells or type 2 innate lymphoid cells (ILC2s) 24‐26 . These cells produce high amounts of cytokines such as IL‐4, IL‐5, and IL‐13 27‐29 .…”