Evolution of the Ikaros Gene Family: Implications for the Origins of Adaptive Immunity

John, Liza B.; Yoong, Simon; Ward, Alister C.

doi:10.4049/jimmunol.0802372

Cited by 27 publications

(13 citation statements)

References 47 publications

(51 reference statements)

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“…They are expressed by different cells (Martín-Ibáñez et al, 2012), and their expression is not modified in the reciprocal knockout mice (Martín-Ibáñez et al, 2010, 2012). These results are contrary to the role of Ikaros family members in the hematopoietic system where they directly interact (Hahm et al, 1998; John et al, 2009), suggesting specific mechanisms of action in each system.…”

Section: Discussioncontrasting

confidence: 84%

“…Ikaros is the founder member of this family of DNA-binding proteins, which consists of Ikaros, Helios (He), Aiolos, Eos and Pegasus (Ikzf1-5, respectively – Mouse Genome Informatics) (John et al, 2009; Rebollo and Schmitt, 2003; Yoshida and Georgopoulos, 2014). In addition, Ikaros has been implicated in CNS development (Agoston et al, 2007; Alsiö et al, 2013; Martín-Ibáñez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

et al. 2017

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Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G1/G0 phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, He−/− mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.

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Section: Discussioncontrasting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

et al. 2017

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“…EtOH = rats prenatally exposed to alcohol DISCUSSION Ikaros family transcription factors are of major importance for hematopoietic development. The model of John et al (2009) places the appearance of the lymphoid Ikaros, Aiolos and Helios proteins coincidentally with the timing of the "emergence" of adaptive immunity at around 450 million years ago (25). In this study we confirm for the first time the expression of all known Ikaros family transcription factors in rat thymic lymphocytes.…”

Section: Monitoring Debilitating Agent S Influence On Development Thrsupporting

confidence: 79%

Ikaros Family Transcription Factors Expression in Rat Thymus: Detection and Impaired Development

Paradžik

Novak

Mokrović

et al. 2012

Int J Immunopathol Pharmacol

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The expression of Ikaros family transcription factors and consequently their signalling pathway is limiting for hematopoietic and lymphocyte development in mice and human. Due to their importance, these transcription factors are highly homologous between species. As an initial approach to examining the possible involvement of Ikaros transcription factors in pathogenesis of rat lymphoid development, we analyzed the expression of all known Ikaros family members, Ikaros, Aiolos, Helios, Eos and Pegasus in the rat thymus. We established a semi-quantitative RT-PCR to detect mRNA of each transcription factor. For the first time we give evidence of the expression of Ikaros family transcription factors in the rat thymus. Further, we evaluated whether their mRNA expression was succumbed to changes when the rats were exposed to ethanol, as a known debilitating agent during development. Therefore we analyzed the thymus of adult rats whose mothers were forced to drink ethanol during gestation, to detect possible changes in thymus mRNA expression levels of Ikaros, Aiolos, Helios, Eos and Pegasus. We found that rats prenatally exposed to ethanol show a slightly higher expression of Ikaros family transcription factors in the adult thymus when compared to control rats, but these differences were not statistically significant. We further studied the distribution of the major lymphocyte subpopulations in the rat thymus according to CD3, CD4 and CD8 expression by four color flow cytometry. We found a higher incidence of CD3 positive cells in the double positive, CD4+CD8+ thymic subpopulation of rats prenatally exposed to ethanol when compared to non-exposed animals. Our findings indicate that ethanol exposure of pregnant rats might influence the development of CD3 positive cells in the thymus of the offspring but this result should be further tackled at the level of transcription factor expression.

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“…A report by Saenz et al (17) described cells with a similar surface phenotype in mesenteric lymph nodes that may have a precursor relationship with myeloid lineages involved in type 2 immunity. In contrast, the IL-13-producing cells we and others describe have properties suggesting a lymphoid lineage, including, as shown here, the shared expression of Aiolos with Th2 cells (33). Further work is certainly needed to understand the interrelationships between these intriguing innate cell populations.…”

Section: Lineage-negative Cells Contribute To Worm Clearance and Tissuementioning

confidence: 62%

Systemically dispersed innate IL-13–expressing cells in type 2 immunity

Price

Liang

Sullivan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

989

1,147

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Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth Nippostrongylus brasiliensis, and they are the major innate IL-13-expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.T ype 2 immune responses are important for the control of infections at mucosal barriers and the development of allergic inflammation. These responses are characterized by eosinophilia, elevated IgE, goblet cell metaplasia with enhanced mucus production, and smooth muscle hyperreactivity, all of which rely critically on production of the canonical type 2-associated cytokines IL-4, IL-5, and IL-13 (1, 2). Although adaptive Th2 cells and follicular T cells are important sources of these cytokines (3), various innate cells, including eosinophils, basophils, and mast cells, have also been implicated as producers of these cytokines in various model systems (1, 2, 4, 5). More recently, the cytokines IL-25 and IL-33, members of the IL-17 and IL-1 cytokine families, respectively, were found to induce type 2 cytokine production when administered to mice, implicating these cytokines in the initiation of type 2 immune responses (6, 7). IL-25 and IL-33 are expressed by epithelial cells, macrophages, and possibly other cell types (8), and they are expressed at elevated levels during infection with parasitic helminths (9, 10) or after challenge with allergens (9, 11). Administration of exogenous IL-25 or IL-33 to mice leads to markedly enhanced levels of IL-4, IL-5, and IL-13 and many of the tissue features of a type 2 immune response (6, 7). Conversely, deficiency in IL-25 leads to diminished IL-4, IL-5, and IL-13 production and variable delays in worm clearance in different helminth models (12, 13). Similarly, mice unable to respond to IL-33 because of deficiency in the T1-ST2 subunit of the IL-33 receptor display diminished Th2-associated cytokines and decreased granuloma formation after injection of Schistosoma mansoni eggs (14).Some of the original descriptions of these cytokines as well as more recent reports have noted the capacity of exogenous ...

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Evolution of the Ikaros Gene Family: Implications for the Origins of Adaptive Immunity

Cited by 27 publications

References 47 publications

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Ikaros Family Transcription Factors Expression in Rat Thymus: Detection and Impaired Development

Systemically dispersed innate IL-13–expressing cells in type 2 immunity

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