PT

Patsharaporn Techasintana

University of Missouri

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Co-Authors

Ulus Atasoy

University of Michigan–Ann Arbor

Joseph Magee

Addenbrooke's Hospital

Matthew M. Gubin

The University of Texas MD Anderson Cancer Center

Robert Calaluce

University of Missouri

Garrett M. Dahm

University of Missouri

Jacqueline Glascock

CURE International UK

Suzanne Ridenhour

University of Missouri

Jason S. Ellis

University of Michigan–Ann Arbor

Matt Gubin

University of Missouri

Jason A. Cascio

University of Iowa Hospitals and Clinics

Cooperative Institutions

University of Missouri

Mahidol University

Siriraj Hospital

University of Missouri Hospital

Johns Hopkins University

National Institutes of Health

University of Missouri Health System

University of Baltimore

Cleveland Clinic Lerner College of Medicine

National Institute on Aging

Author Statistics

Papers

Citation

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RNA binding protein HuR posttranscriptionally regulates antigen-specific T cell proliferation and allergen induced airway inflammation

The Journal of Immunology (2016)

Jason S. Ellis Patsharaporn Techasintana Jacqueline Glascock Suzanne Ridenhour Ulus Atasoy

Abstract RNA binding protein HuR (ELAVL1) governs transcript stability of IL-4, IL-13 and GATA-3 mRNAs, thereby controlling Th2 differentiation. We hypothesized that HuR plays a role in antigen induced T cell activation and initiation of allergic airway inflammation. We conditionally ablated HuR in T cells prior to activation (distal lck-Cre ROSA HuRfl/fl mouse). Half of mature CD4+ T cells were HuR deficient in these mice. To determine the effects of HuR KO in T cells, mice were immunized with OVA, boosted 10 days later, and antigen specific proliferative responses were measured in vitro. Despite being fully capable of proliferation upon anti-CD3/CD28 stimulation, YFP+ (HuR KO) T cells were unable to proliferate in response to antigen while YFP− control cells had no proliferative defects. We then used the OVA challenge model of airway inflammation to ascertain effects of HuR KO in vivo. HuR KO mice had significantly less total cellular inflammation, as well as significant reductions in BAL IL-13. To determine the mechanism of suppression, we conducted in vitro activation experiments. HuR KO CD4+ T cells were sorted into YFP+ and YFP− pools and activated. YFP+ T cells had significant decreases in IL-4, IL-5, IL-13 but not IFNγ protein. Gata-3, IL-4 and IL-2Ra (CD25) transcription were significantly reduced. KO T cells have reductions in pSTAT5 signaling which is required for robust Th2 differentiation. While only 50% of CD4+ T cells lack HuR, there was total suppression of Th2 differentiation in airway inflammation. These data elucidate a critical role for HuR in regulating Th2 differentiation and allergic airway inflammation.

Allergic Inflammation

10.4049/jimmunol.196.supp.191.18

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Conditional Knockout of the RNA-Binding Protein HuR in CD4+ T Cells Reveals a Gene Dosage Effect on Cytokine Production

Molecular Medicine (2014)

Matthew M. Gubin Patsharaporn Techasintana Joseph Magee Garrett M. Dahm Robert Calaluce

The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation. Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression. By using a novel conditional HuR knockout (KO) mouse in which HuR is deleted in activated T cells, we show that Th2-polarized cells from heterozygous HuR conditional (OX40-Cre HuRfl/+) KO mice had decreased steady-state levels of Gata3, Il4 and Il13 mRNAs with little changes at the protein level. Surprisingly, Th2-polarized cells from homozygous HuR conditional (OX40-Cre HuRfl/fl) KO mice showed increased Il2, Il4 and Il13 mRNA and protein via different mechanisms. Specifically, Il4 was transcriptionally upregulated in HuR KO T cells, whereas Il2 and Il13 mRNA stabilities increased. Additionally, when using the standard ovalbumin model of allergic airway inflammation, HuR conditional KO mice mounted a robust inflammatory response similar to mice with wild-type HuR levels. These results reveal a complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role. These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection.

GATA3

Knockout mouse

Conditional gene knockout

10.2119/molmed.2013.00127

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Citations (32)

An impact on medical student knowledge outcomes after replacing peer lectures with small group discussions

MedEdPublish (2019)

Korakit Imwattana Pattarachai Kiratisin Patsharaporn Techasintana Popchai Ngamskulrungroj

This article was migrated. The article was marked as recommended. Active learning has been proven as an effective teaching method that increases students' academic performance, satisfaction, and promotes life-long learning. A previous study showed that a peer lecture was time-consuming for both faculty members and students without any increase in knowledge outcome achievement of students when comparing to faculty lectures. Therefore, we replaced all peer teachings, taught in 2015, with faculty lectures and small group discussions in an organ-system part which focused mainly on applications of medical microbiology in 2016. The organ-system part was further divided into 3 sections according to type of organ systems. The knowledge outcome achievement was compared using MCQ scores. Peer lectures were mainly used as a teaching method only in 2015 (91.5%, 43 hours from a total of 47 hours) while none of them was used in 2016. On the other hand, SDG were mainly used as a teaching method only in 2016 (73.9%, 51 hours from a total of 69 hours). Students of 2016 had significantly higher average MCQ scores than those of 2015 only in the section 3 (80.8% as compared with 60.5%; p value < 0.001). There was no significant difference in section 1, section 2, and overall MCQ scores. Apart from routine teaching preparation, there was no out-of-class preparation time for faculty lectures and SGD while peer teaching required at least 0.5-2 hours of extra out-of-class preparation time from at least 1 faculty member and 10-12 students per 1 hour of teaching. In conclusion, SGD provided equal or more knowledge outcome achievement of the student with less time-consuming than peer lecture. Therefore, at least in our teaching environment, SGD was proved to be a better option than a peer lecture for teaching applications of medical microbiology.

Class size

10.15694/mep.2018.0000224.2

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Citations (2)

Immunocompromised Group Differences in the Presentation of Intestinal Strongyloidiasis

Japanese Journal of Infectious Diseases (2008)

Premjit Vaiyavatjamai John J. Boitano Patsharaporn Techasintana Anchalee Tungtrongchitr

The hospital records of 213 outpatients from Bangkok, Thailand, infected with Strongyloides stercoralis as determined by stool inspections were examined retrospectively for the different clinical presentations ascribed to patients with HIV, those with chronic illness, those who used immunosuppressant drugs and relatively healthy subjects. For HIV patients with strongyloidiasis, the most common symptoms were chronic diarrhea, fever, persistent coughing and loss of weight, but only the first three symptoms were significantly different from other immunocompromised hosts. For healthy patients with strongyloidiasis, acute diarrhea and abdominal pain were the most frequent symptoms. Moreover, the peripheral eosinophil blood count was significantly lower (P = 0.004) in the HIV patients than in any of the other subsets. Males were more common than females across all categories. While the average age of all subjects was 48.3 ± 16.4 years, the strongyloidiasis patients with chronic illness were significantly older (56.8 ± 13.5 years) than those in the other groups. This study may suggest that strongyloidiasis is commonly found in geriatric males, and that the patients most at risk for S. stercoralis infection are HIV patients. This is the first report of the different clinical presentations of intestinal strongyloidiasis in various groups of patients with impaired immunity.

Strongyloidiasis

Presentation (obstetrics)

10.7883/yoken.jjid.2008.5

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Citations (22)

The RNA-binding protein HuR is a posttranscriptional on switch for CD4+ Th2 and Th17 differentiation (LYM3P.730)

The Journal of Immunology (2014)

Ulus Atasoy Jing Chen Patsharaporn Techasintana Matthew M. Gubin Joseph Magee

Abstract Posttranscriptional control by RNA binding proteins (RBPs) in CD4+ T cells is poorly understood. The RBP, HuR, regulates IL-4, IL-13 and GATA-3, by binding to AU-rich (ARE) regions in their 3’ UTRs. We hypothesized HuR is regulating CD4+ Th2 differentiation by controlling mRNA stability. We previously showed that HuR over-expression results in increased Th2 differentiation and Th2 cytokines. We generated a new model to study Th2 differentiation, distal Lck-cre ROSA HuRfl/fl, in which HuR is ablated prior to T cell activation. This resulted in profound suppression of Th2 but not Th1 cytokines, under in vitro conditions. We used the ova challenge model of airway inflammation to study antigen presentation and in vivo cytokine regulation. HuR KO mice had completely abolished lung cellular inflammation to levels similar to non-immunized mice. This further resulted in significant reductions in IL-4, IL-13 secretion, and serum IgE levels. We also investigated effects of HuR ablation in Th17 differentiation. We show HuR regulates IL-17 expression by controlling transcript stability. HuR KO T cells have greatly reduced Th17 differentiation (66% reduction) and diminished onset and severity of inflammation in an EAE model. These data indicate that HuR is required for efficient CD4+ Th2 and Th17 differentiation both in vitro and in vivo but not Th1. These findings reveal nuanced control by HuR upon different CD4+ T cell subsets.

10.4049/jimmunol.192.supp.64.4

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The RNA-Binding Protein HuR Posttranscriptionally Regulates IL-2 Homeostasis and CD4+ Th2 Differentiation

ImmunoHorizons (2017)

Patsharaporn Techasintana Jason S. Ellis Jacqueline Glascock Matthew M. Gubin Suzanne Ridenhour

Abstract Posttranscriptional gene regulation by RNA-binding proteins, such as HuR (elavl1), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3′ untranslated region adenylate and uridylate–rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization. However, its effects upon IL-2 homeostasis and CD4+ Th2 differentiation are not as well understood. We found that optimal translation of Il2ra (CD25) required interaction of its mRNA with HuR. Conditional HuR knockout in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in JAK–STAT signaling, Th2 differentiation, and cytokine production. HuR-knockout CD4+ T cells from OVA-immunized mice also failed to proliferate in response to Ag. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis and initiating CD4+ Th2 differentiation.

Homeostasis

AU-rich element

10.4049/immunohorizons.1700017

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Citations (19)

Transcriptomic-Wide Discovery of Direct and Indirect HuR RNA Targets in Activated CD4+ T Cells

PLoS ONE (2015)

Patsharaporn Techasintana J. Wade Davis Matthew M. Gubin Joseph Magee Ulus Atasoy

Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs) and microRNAs (miRNAs). RNA immunoprecipitation (RIP) methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1) and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads) that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads) to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms.

10.1371/journal.pone.0129321

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Citations (13)

Posttranscriptional Gene Regulation of IL-17 by the RNA-Binding Protein HuR Is Required for Initiation of Experimental Autoimmune Encephalomyelitis

The Journal of Immunology (2013)

Jing Chen Jason A. Cascio Joseph Magee Patsharaporn Techasintana Matthew M. Gubin

IL-17 is a proinflammatory cytokine produced by activated Th17 cells and other immune cells. IL-17-producing Th17 cells are major contributors to chronic inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although the transcriptional regulation of Th17 cells is well understood, the posttranscriptional regulation of IL-17 gene expression remains unknown. The RNA-binding protein HuR positively regulates the stability of many target mRNAs via binding the AU-rich elements present in the 3' untranslated region of many inflammatory cytokines including IL-4, IL-13, and TNF-α. However, the regulation of IL-17 expression by HuR has not been established. CD4(+) Th17 cells from HuR knockout mice had decreased IL-17 steady-state mRNA and protein levels compared with wild-type Th17 cells, as well as decreases in frequency of IL-17(+) cells. Moreover, we demonstrated that HuR directly binds to the IL-17 mRNA 3' untranslated region by using RNA immunoprecipitation and biotin pulldown assays. In addition, the knockout of HuR decreased cellular proliferation of CD4(+) T cells. Mice with adoptively transferred HuR KO Th17 cells had delayed initiation and reduced disease severity in the onset of experimental autoimmune encephalomyelitis compared with wild-type Th17 cells. Our results reveal a HuR-induced posttranscriptional regulatory mechanism of Th17 differentiation that influences IL-17 expression. These findings may provide novel therapeutic targets for the treatment of Th17-mediated autoimmune neuroinflammation.

AU-rich element

Knockout mouse

Proinflammatory cytokine

Gene knockout

10.4049/jimmunol.1301188

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Citations (71)

RNA-Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Normal IL-2 Homeostasis and Allergic Airway Inflammation

Journal of Allergy and Clinical Immunology (2016)

Ulus Atasoy Patsharaporn Techasintana Jacqueline Glascock Suzanne Ridenhour Joseph Magee

Allergic Inflammation

10.1016/j.jaci.2015.12.710

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Citations (1)

ANALYSIS OF IgE-BINDING ALLERGENS IN CULEX QUINQUEFASCIATUS SALIVA PROTEIN IN MOSQUITO BITE ALLERGIC PATIENTS

Annals of Allergy Asthma & Immunology (2007)

Sirichit Wongkamchai Patsharaporn Techasintana Wanee Wisuthsarewong Kanokvalai Kulthanan Puan Suthipinittharm

Culex quinquefasciatus

10.1016/s1081-1206(10)60698-9

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Citations (11)