IL33 and Type 2 Innate Lymphoid Cells (ILC2) But Not Th2 Cells Are Essential For Persistence Of Chronic Experimental Asthma

Christianson, Christina A.; Irvin, Chaoyu; Górska, M.; Alam, Rafeul

doi:10.1016/j.jaci.2013.12.610

Cited by 5 publications

(3 citation statements)

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“…In mice, two distinct ILC2 populations have been characterized: natural ILC2s that are identified as Lineage - ST2 + KLRG1 int and classified as homeostatic, tissue-resident and IL-33-responsive; and, inflammatory ILC2s, which are undetectable at the steady-state but expand in response to IL-25 and can be distinguished as Lineage - ST2 - KLRG1 hi cells ( 42 ). ILC2s are activated by IL-33, IL-25, thymic stromal lymphopoietin (TSLP) and other danger signals produced by the airway epithelium ( 43 , 44 ), with further support from prostaglandin D 2 signalling through the CRTH2 receptor ( 40 ). Additionally, p38 MAPK has been found to positively regulate ILC2 function ( 45 ) while TGF-β is thought to program development via induction of ST2 expression in ILC2 progenitors ( 46 ).…”

Section: Phenotypic Features Of Ilc Subsetsmentioning

confidence: 99%

The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

et al. 2021

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The lung is a vital mucosal organ that is constantly exposed to the external environment, and as such, its defenses are continuously under threat. The pulmonary immune system has evolved to sense and respond to these danger signals while remaining silent to innocuous aeroantigens. The origin of the defense system is the respiratory epithelium, which responds rapidly to insults by the production of an array of mediators that initiate protection by directly killing microbes, activating tissue-resident immune cells and recruiting leukocytes from the blood. At the steady-state, the lung comprises a large collection of leukocytes, amongst which are specialized cells of lymphoid origin known as innate lymphoid cells (ILCs). ILCs are divided into three major helper-like subsets, ILC1, ILC2 and ILC3, which are considered the innate counterparts of type 1, 2 and 17 T helper cells, respectively, in addition to natural killer cells and lymphoid tissue inducer cells. Although ILCs represent a small fraction of the pulmonary immune system, they play an important role in early responses to pathogens and facilitate the acquisition of adaptive immunity. However, it is now also emerging that these cells are active participants in the development of chronic lung diseases. In this mini-review, we provide an update on our current understanding of the role of ILCs and their regulation in the lung. We summarise how these cells and their mediators initiate, sustain and potentially control pulmonary inflammation, and their contribution to the respiratory diseases chronic obstructive pulmonary disease (COPD) and asthma.

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Section: Phenotypic Features Of Ilc Subsetsmentioning

confidence: 99%

The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

et al. 2021

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“…Blockade of IL-33 signalling has been shown to limit the development of ILC2-mediated chronic asthma (63), with the administration of IL-33 activating ILC2-dependent lung inflammatory responses and goblet cell hyperplasia (12). Similar to our results with papain, intranasal treatment of c-Rel-deficient mice with rIL-33 also resulted in reduced eosinophilia and lower expression of Il5 and Il13 in the lungs.…”

Section: Discussionmentioning

confidence: 99%

c-Rel is required for IL-33-dependent activation of ILC2s

Zaini

Fulford

Grumont

et al. 2021

Preprint

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Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient mice resistant to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.

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“…Expression of Il33 or Il1rl1 genes also correlates with susceptibility to asthma (19,(60)(61)(62), as well as the type 2 response in murine experimental asthma models (2,58,59), further supporting a crucial role of IL-33mediated ILC2s activation during allergy. In addition, blockade of IL-33 signaling has been shown to limit the development of ILC2-mediated chronic asthma (63), with the administration of IL-33 activating ILC2-dependent lung inflammatory responses and goblet cell hyperplasia (12). As the loss of c-Rel impairs ex vivo IL-33-dependent ILC2 proliferation and expansion, we questioned whether c-Rel could also be responsible for ILC2mediated allergic lung responses.…”

Section: Discussionmentioning

confidence: 99%

c-Rel Is Required for IL-33-Dependent Activation of ILC2s

et al. 2021

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Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient (c-Rel–/–) mice present a significantly reduced response to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.

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IL33 and Type 2 Innate Lymphoid Cells (ILC2) But Not Th2 Cells Are Essential For Persistence Of Chronic Experimental Asthma

Cited by 5 publications

References 0 publications

The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases

c-Rel is required for IL-33-dependent activation of ILC2s

c-Rel Is Required for IL-33-Dependent Activation of ILC2s

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