Crosstalk between ILC2s and Th2 cells varies among mouse models

Gurram, Rama Krishna; Wei, Danping; Yu, Qiao; Butcher, Matthew J.; Chen, Xi; Cui, Kairong; Hu, Gangqing; Zheng, Mingzhu; Zhu, Xiaoliang; Oh, Jangsuk; Sun, Bing; Urban, Joseph F.; Zhao, Keji; Zhu, Jinfang

doi:10.1016/j.celrep.2023.112073

Cited by 20 publications

(26 citation statements)

References 52 publications

(65 reference statements)

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“…Adoptive transfer experiments of ILC2s in lymphopenic or immunodeficient mice did rescue defects to expel the parasite, and therefore provide additional evidence for a pivotal role of ILC2s (9,28). Complete depletion of ILC2 using Nmur1 iCre-eGFP Ild2 flox/flox , Nmur1 iCre-eGFP Gata3 flox/flox or Klrg1 Cre Gata3 flox/flox resulted in a severe defect in worm expulsion demonstrating the essential role of ILC2 for resistance to N. brasiliensis infection (21,48). IL-25R and ST2 fulfill complementary functions to trigger ILC2 activation since genetic ablation of both receptors resulted in a comparable phenotype to ILC2-deficient mice characterized by strongly delayed worm expulsion and ongoing worm infection until day 14 -20 post infection (28).…”

Section: Discussionmentioning

confidence: 84%

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

et al. 2023

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The initiation of type 2 immune responses at mucosal barriers is regulated by rapidly secreted cytokines called alarmins. The alarmins IL-33, IL-25 and TSLP are mainly secreted by stromal and epithelial cells in tissues and were linked to chronic inflammatory diseases, such as allergic lung inflammation, or to resistance against worm infections. Receptors for alarmins are expressed by a variety of immune cells, including group 2 innate lymphoid cells (ILC2s), an early source of the type 2 cytokines, such as IL-5 and IL-13, which have been linked to atopic diseases and anti-worm immunity as well. However, the precise contribution of the IL-33 receptor signals for ILC2 activation still needs to be completed due to limitations in targeting genes in ILC2. Using the newly established Nmur1iCre-eGFP mouse model, we obtained specific conditional genetic ablation of the IL-33 receptor subunit ST2 in ILC2s. ST2-deficient ILC2s were unresponsive to IL-33 but not to stimulation with the alarmin IL-25. As a result of defective ST2 signals, ILC2s produced limited amounts of IL-5 and IL-13 and failed to support eosinophil homeostasis. Further, ST2-deficient ILC2s were unable to expand and promote the recruitment of eosinophils during allergic lung inflammation provoked by papain administration. During infection with Nippostrongylus brasiliensis, ILC2-intrinsic ST2 signals were required to mount an effective type 2 immune response against the parasite leading to higher susceptibility against worm infection in conditional knockout mice. Therefore, this study argues for a non-redundant role of cell-intrinsic ST2 signals triggering proper activation of ILC2 for initiation of type 2 immunity.

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Section: Discussionmentioning

confidence: 84%

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

et al. 2023

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“…However, because of the abnormal thymic differentiation of tdKO cells, such experiments could not properly evaluate the role of Zfp281 and Zfp148 during T H 2 differentiation. To overcome this limitation, we performed gene deletion using a CD2 -Cre transgene active in postthymic T cells ( 53 ) but not in type 2 innate lymphoid cells ( 54 ). We generated Zfp281 fl/fl Zfp148 fl/fl CD2 -Cre mice (pdKO), in which we also introduced a Rosa26 YFP allele, expressing yellow fluorescent protein (YFP) after Cre-mediated recombination; subsequent analyses were gated on YFP + pdKO cells.…”

Section: Resultsmentioning

confidence: 99%

Zfp281 and Zfp148 control CD4 ⁺ T cell thymic development and T _H 2 functions

Chopp,

Zhu,

Gao

et al. 2023

Sci. Immunol.

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How CD4 + lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (T H 2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4 + T cell differentiation of class II major histocompatibility complex (MHC II)–restricted thymocytes, including expression of the CD4 + lineage–committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of T H 2 cytokine genes but not of the T H 2 lineage–determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and T H 2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4 + T cell development and T H 2 cell responses.

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“…Although several previous reports showed a degree of functional redundancy between ILC2s and Th2 cells, 10,11 emerging evidence has demonstrated that they each have specialized functions and can cooperate with each other during infection and allergic inflammation 11–14 . For instance, in some circumstances, ILC2s are essential for initial local priming of Th2 responses 10,15,16 . In return, Th2 cells can enhance ILC2 response by inducing the expression of IL‐25 and IL‐33 10 .…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14] For instance, in some circumstances, ILC2s are essential for initial local priming of Th2 responses. 10,15,16 In return, Th2 cells can enhance ILC2 response by inducing the expression of IL-25 and IL-33. 10 Abundant studies have found that ILC2 development and function are regulated by multiple factors, including transcription factors, cytokines, lipid mediators, hormones, neurotransmitters and cell surface molecules.…”

Section: Introductionmentioning

confidence: 99%

“…10,15,16 In return, Th2 cells can enhance ILC2 response by inducing the expression of IL-25 and IL-33. 10 Abundant studies have found that ILC2 development and function are regulated by multiple factors, including transcription factors, cytokines, lipid mediators, hormones, neurotransmitters and cell surface molecules. 17,18 Of note, in recent years, the role of hormones in regulating ILC2 response during allergic lung inflammation has been extensively studied (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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The role of hormones in ILC2‐driven allergic airway inflammation

Dai,

Gong,

Wang

et al. 2024

Scand J Immunol

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Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL‐5 and IL‐13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial‐derived alarmins, such as IL‐33, IL‐25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2‐driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.

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Crosstalk between ILC2s and Th2 cells varies among mouse models

Cited by 20 publications

References 52 publications

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

Zfp281 and Zfp148 control CD4 ⁺ T cell thymic development and T _H 2 functions

The role of hormones in ILC2‐driven allergic airway inflammation

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Crosstalk between ILC2s and Th2 cells varies among mouse models

Cited by 20 publications

References 52 publications

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses

Zfp281 and Zfp148 control CD4 + T cell thymic development and T H 2 functions

The role of hormones in ILC2‐driven allergic airway inflammation

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Zfp281 and Zfp148 control CD4 ⁺ T cell thymic development and T _H 2 functions