<i>CISH</i>and Susceptibility to Infectious Diseases

Khor, Chiea‐Chuen; Vannberg, Fredrik; Chapman, S. Jonathan; Guo, Hongyu; Wong, Sunny H.; Walley, Andrew J.; Vukcevic, Damjan; Rautanen, Anna; Mills, Tara C.; K-C., Chang; Kam, Korey; Crampin, Amelia C.; Ngwira, Bagrey; C-C., Leung; Tam, CM; Chan, Chieh‐Kai; Sung, Joseph J.Y.; Ww, Yew; Toh, Kai Yee; Tay, Stacey K.H.; Kwiatkowski, Dominic P.; Lienhardt, Christian; Hien, TT; Day, Nicholas P. J.; Peshu, N; Marsh, Kevin; Maitland, Kathryn; Scott, John A.; Williams, Thomas N.; Berkley, James A.; Floyd, Sian; Tang, Nelson L.S.; Pe, Fine; Dlm., Goh; Avs., Hill

doi:10.1056/nejmoa0905606

Cited by 124 publications

(99 citation statements)

References 40 publications

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“…In recent years there has been a marked increase in our understanding of how SNPs in the human genome contribute to many diseases, including susceptibility to particular infections such as tuberculosis and leprosy (55,56). However, the role that microbial SNPs play in human infection is only beginning to be appreciated (14).…”

Section: Discussionmentioning

confidence: 99%

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Carroll¹,

Shelburne²,

Olsen³

et al. 2011

J. Clin. Invest.

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Infection with different strains of the same species of bacteria often results in vastly different clinical outcomes. Despite extensive investigation, the genetic basis of microbial strain-specific virulence remains poorly understood. Recent whole-genome sequencing has revealed that SNPs are the most prevalent form of genetic diversity among different strains of the same species of bacteria. For invasive serotype M3 group A streptococci (GAS) strains, the gene encoding regulator of proteinase B (RopB) has the highest frequency of SNPs. Here, we have determined that ropB polymorphisms alter RopB function and modulate GAS host-pathogen interactions. Sequencing of ropB in 171 invasive serotype M3 GAS strains identified 19 distinct ropB alleles. Inactivation of the ropB gene in strains producing distinct RopB variants had dramatically divergent effects on GAS global gene expression. Additionally, generation of isoallelic GAS strains differing only by a single amino acid in RopB confirmed that variant proteins affected transcript levels of the gene encoding streptococcal proteinase B, a major RopB-regulated virulence factor. Comparison of parental, RopB-inactivated, and RopB isoallelic strains in mouse infection models demonstrated that ropB polymorphisms influence GAS virulence and disease manifestations. These data detail a paradigm in which unbiased, whole-genome sequence analysis of populations of clinical bacterial isolates creates new avenues of productive investigation into the pathogenesis of common human infections.

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Section: Discussionmentioning

confidence: 99%

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Carroll¹,

Shelburne²,

Olsen³

et al. 2011

J. Clin. Invest.

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“…Moreover, Nakajima et al (49) showed that expression of both Cish mRNA and protein is significantly increased in allergen-stimulated CD4 + T cells from hen egg-allergic patients relative to patients not allergic to hen eggs. In addition, Khor et al (50) identified a panel of Cish single nucleotide polymorphisms associated with increased susceptibility to infectious diseases, such as bacteremia, malaria, and tuberculosis. Thus, Cish expression caused by demethylation within the Cish locus in memory T cells may play a role in some infectious and allergic diseases.…”

Section: Downloaded Frommentioning

confidence: 99%

Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells

Hashimoto

Ogoshi

Sasaki

et al. 2013

The Journal of Immunology

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Memory CD4+ T cells are central regulators of both humoral and cellular immune responses. T cell differentiation results in specific changes in chromatin structure and DNA methylation of cytokine genes. Although the methylation status of a limited number of gene loci in T cells has been examined, the genome-wide DNA methylation status of memory CD4+ T cells remains unexplored. To further elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses of memory CD4+ T cells generated using T cells from TCR-transgenic mice. The resulting genome-wide DNA methylation profile revealed 1144 differentially methylated regions (DMRs) across the murine genome during the process of T cell differentiation, 552 of which were associated with gene loci. Interestingly, the majority of these DMRs were located in introns. These DMRs included genes such as CXCR6, Tbox21, Chsy1, and Cish, which are associated with cytokine production, homing to bone marrow, and immune responses. Methylation changes in memory T cells exposed to specific Ag appeared to regulate enhancer activity rather than promoter activity of immunologically relevant genes. In addition, methylation profiles differed between memory T cell subsets, demonstrating a link between T cell methylation status and T cell differentiation. By comparing DMRs between naive and Ag-specific memory T cells, this study provides new insights into the functional status of memory T cells.

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“…Other mechanisms that may contribute to this transient phenotype remain to be determined, and the role of the cish.b paralog awaits further study. Moreover, recent studies have also implicated the human CISH gene as a susceptibility locus for several infectious agents (22), and suggested that CISH contributes to expansion of regulatory T cells in response to microbial infection (66). Therefore, further analysis of the role of CISH in immunity represents an exciting area for future research.…”

Section: Discussionmentioning

confidence: 99%

“…An alternate transgenic mouse model in which CISH was expressed in a T cell-specific manner indicated an independent role in TCR signaling (20). Meanwhile, increased susceptibility to infectious diseases has recently been associated with polymorphisms in the human CISH promoter, which blunted CISH induction following IL-2 stimulation (22).…”

mentioning

confidence: 99%

Regulation of Embryonic Hematopoiesis by a Cytokine-Inducible SH2 Domain Homolog in Zebrafish

Lewis

Noor

Fraser

et al. 2014

The Journal of Immunology

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Cytokine-inducible SH2 domain–containing protein (CISH), a member of the suppressor of cytokine signaling family of negative feedback regulators, is induced by cytokines that activate STAT5 and can inhibit STAT5 signaling in vitro. However, demonstration of a definitive in vivo role for CISH during development has remained elusive. This study employed expression analysis and morpholino-mediated knockdown in zebrafish in concert with bioinformatics and biochemical approaches to investigate CISH function. Two zebrafish CISH paralogs were identified, cish.a and cish.b, with high overall conservation (43–46% identity) with their mammalian counterparts. The cish.a gene was maternally derived, with transcripts present throughout embryogenesis, and increasing at 4–5 d after fertilization, whereas cish.b expression commenced at 8 h after fertilization. Expression of cish.a was regulated by the JAK2/STAT5 pathway via conserved tetrameric STAT5 binding sites (TTCN3GAA) in its promoter. Injection of morpholinos targeting cish.a, but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a 2- 3-fold increase in erythrocytic markers. This occurred concomitantly with increased activation of STAT5. This study indicates that CISH functions as a conserved in vivo target and regulator of STAT5 in the control of embryonic hematopoiesis.

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CISHand Susceptibility to Infectious Diseases

Cited by 124 publications

References 40 publications

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice

Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells

Regulation of Embryonic Hematopoiesis by a Cytokine-Inducible SH2 Domain Homolog in Zebrafish

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