The Transcription Factor STAT3 Is Required for T Helper 2 Cell Development

Stritesky, Gretta L.; Muthukrishnan, Rajarajeswari; Sehra, Sarita; Goswami, Ritobrata; Pham, Duy; Travers, Jared; Nguyen, Evelyn T.; Levy, David E.; Kaplan, Mark H.

doi:10.1016/j.immuni.2010.12.013

Cited by 198 publications

(179 citation statements)

References 60 publications

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“…BATF is clearly downstream of STAT3 in Th17 and Th2 cells (20,21) and, as shown here, is downstream of STAT6 in Th9 cells. Both of these STAT proteins are required for Th2 development, but despite this reliance, there are conflicting data on whether BATF is required for Th2 development (13,15).…”

Section: Th9 Cells Have a Distinct Transcriptional Signaturesupporting

confidence: 73%

Th9 cell development requires a BATF-regulated transcriptional network

Jabeen¹,

Goswami²,

Awe³

et al. 2013

J. Clin. Invest.

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196

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T helper 9 (Th9) cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor-like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.

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Section: Th9 Cells Have a Distinct Transcriptional Signaturesupporting

confidence: 73%

Th9 cell development requires a BATF-regulated transcriptional network

Jabeen¹,

Goswami²,

Awe³

et al. 2013

J. Clin. Invest.

Self Cite

196

233

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“…For instance, AR inhibits IL12 signaling and Th1 cell differentiation by up-regulating Ptpn1 (Kissick et al, 2014), STAT3 activation and HIF1α inhibit iTreg cell differentiation (Laurence et al, 2012;Palazon et al, 2014), and ETV6 is known as a repressor in Th17 cells (Ciofani et al, 2012). However, STAT3 can also induce Th17 cell differentiation (Zhu and Paul, 2010) and promote Th2 cell differentiation together with IL6 (Stritesky et al, 2011).…”

Section: Th2 Cell-specific Tfs Are Positively Regulated By Stat6 and mentioning

confidence: 99%

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

et al. 2016

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ABSTRACT. Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.

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“…Furthermore, STAT5A/B increases Th1 responses by regulating T-box transcription factor (TBX21) and interleukin-12 receptor subunit beta-2 (IL12Rβ2) [58]. Interestingly, STAT3 takes part in Th2 differentiation and binds to Th2-associated gene loci [59].…”

Section: Jak/stat Pathway and Cytokines In Msmentioning

confidence: 99%

JAK-STAT Lodges in Multiple Sclerosis: Pathophysiology and Therapeutic Approach Overview

Hamid¹,

Isiyaku²,

Kalgo³

et al. 2017

OALib

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Multiple sclerosis (MS) is a complex inflammatory and demyelinating disease of central nervous system (CNS). The disease pathogenesis is not fully understood and no actual cure for the disease yet. The disease has genetic and environmental cause as fundamental factors which are identified for the disease pathogenesis so far. One of the characteristic features of the disease is inflammation cause due to activation of pro-inflammatory cells. Interference in signalling pathways such as JAK/STAT could result in physiological or pathological outcome in MS. Dysregulation of JAK/STAT signalling pathway is associated with chronic inflammatory process and immune disorders. In this review, considering the important role of JAK/STAT pathway in signal transduction of inflammatory process and immune responses in CNS, we describe the involvement of this signal transduction pathway in MS. Moreover, we consider the physiological and pathological involvement of JAK/STAT rout in neurogenesis/gliogenesis, cytokines production and as therapeutics target for managing MS.

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The Transcription Factor STAT3 Is Required for T Helper 2 Cell Development

Cited by 198 publications

References 60 publications

Th9 cell development requires a BATF-regulated transcriptional network

Th9 cell development requires a BATF-regulated transcriptional network

Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions

JAK-STAT Lodges in Multiple Sclerosis: Pathophysiology and Therapeutic Approach Overview

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