Sony Pixel Power calrec Sony

New Understanding of Tiny RNA Molecules Could Have Medical Applications from Viral Vaccines to Treatments for Autoimmune Diseases

30/06/2013

New Understanding of Tiny RNA Molecules Could Have Medical Applications from Viral Vaccines to Treatments for Autoimmune Diseases LA JOLLA, CA June 30, 2013 A team led by scientists at The Scripps Research Institute (TSRI) has identified a family of tiny RNA molecules that work as powerful regulators of the immune response in mammals. Mice who lack these RNA molecules lose their normal infection-fighting ability, whereas mice that overproduce them develop a fatal autoimmune syndrome.

This finding gives us insights into immune regulation that could be very helpful in a range of medical applications, from viral vaccines to treatments for autoimmune diseases, said Changchun Xiao, assistant professor in TSRI's Department of Immunology and Microbial Science and senior investigator for the study, which appears in the June 30, 2013 issue of Nature Immunology.

Unraveling a Crucial Process

The finding concerns a key interaction between T cells and B cells, the allied lymphocyte armies that make up most of the adaptive immune system of mammals. B cells, which produce antibodies, usually lie in wait for pathogens in special zones called follicles within lymph nodes and the spleen. But to start proliferating normally and pumping out antibodies to fight an infection, these B cells have to be assisted, in effect, by T cells known as follicular helper T cells (TFH cells). The TFH cells have to migrate into the B cell follicles and physically contact the B cells in order to provide help to them, said Xiao. However, the molecular pathways that control TFH cell differentiation and migration have not been well understood.

In 2009, other researchers proposed that this crucial process requires the suppression of the miR-17 92 family of RNA molecules. These are among the thousands of short RNA molecules (often known as micro-RNAs, miRs, or miRNAs) that are made by mammalian cells and are meant to do their jobs while in RNA form. Typically an miRNA works inside the cell as a basic regulator or dimmer switch for the activity of tens to hundreds of genes it binds to transcripts of those genes and slows down their translation into proteins.

Xiao, who had been studying the miR-17 92 family since 2005, decided to examine their role in TFH differentiation. His team began by measuring the levels of these miRNAs in young, na ve T cells and in the TFH cells to which these T cells gave birth after exposure to foreign antigens.

Surprising Finding

To the researchers' surprise, the miR-17 92s showed the opposite pattern of expression than expected: their levels jumped as the na ve T cells began differentiating into TFH cells, but fell back by the time the process was finished. The finding suggested that, far from acting as a brake on TFH differentiation, miR-17 92s work as enablers of the process.

To confirm their suspicion, team members developed mutant mouse lines in which some or all of the miR-17 92 miRNAs were knocked out of T cells. These miR-17 92-deficient T cells turned out to be much less able to differentiate into TFH cells. As a result, the follicle-dwelling B cells that depend on TFH assistance also lost much of their ability to respond to an immune challenge. These mutant mice showed a deficient antibody response to a standard immune-provoking protein, said Seung Goo Kang, a postdoctoral research associate in the Xiao laboratory who was the leading author of the study.

Collaborating TSRI scientists led by John Teijaro, a senior research associate in the laboratory of Michael B. A. Oldstone, professor in the Department of Immunology and Microbial Science, showed further that these transgenic mice unlike ordinary lab mice could not clear a chronic virus infection that is used as a standard challenge in immunological experiments.

By contrast, when the team raised transgenic mice whose T cells produced four to six times the normal amount of miR-17 92s, these T cells differentiated into TFH cells spontaneously that is, without an immune-stimulating inoculation. These mice developed antibody responses to their own tissues, and died young, with swollen spleen and lymph nodes. The accumulation of autoantibodies is also seen in lupus and other autoimmune diseases in humans, said Wen-Hsien Liu, another postdoctoral research associate in the Xiao laboratory and a co-first author of the paper.

Important Targets

Liu and Kang were able to track down a key target gene of miR-17 92s, which the miRNAs suppress to enable TFH cell differentiation. The targeted gene codes for Phlpp2, a recently discovered signaling inhibitor. Lowering Phlpp2 protein levels in our miR-17 92-knockout T cells restored much of their ability to become TFH cells, Kang said.

Phlpp2 is one important target, but we believe there are others too, and we are now looking for those, Xiao said. He and his colleagues also plan to investigate methods for manipulating miR-17 92s and their TFH cell-related pathways, in order to boost antibody responses to vaccines for example or alternatively to lower autoantibody productions in people with autoimmune diseases.

The study, miR-17 92 family microRNAs are critical regulators of T follicular helper cell differentiation, was a collaboration that also involved the laboratory of Hai Qi at Tsinghua University in Beijing and the laboratory of Eric Verdin at the Gladstone Institute of Virology and Immunology at the University of California, San Francisco. A co-first author of the study was Peiwen Lu of the Qi laboratory; other co-authors were Hyung W. Lim of the Verdin laboratory, Daniel Fremgen of the Oldstone laboratory and Hyun Yong Jin and Jovan Shepherd of the Xiao laboratory.

The study was funded by the PEW Charitable Trusts, the Cancer Research Institute, the Lupus Research Institute, the American Heart Association (grant 11POST7430106 ), the National Institutes of He
LINK: http://www.scripps.edu/news/press/2013/20130630xaio.html...
See more stories from scripps

Most recent headlines

13/03/2025

You Will Leave Opus Singing the Original Bops Performed by John Malkovich

(L-R) Stephanie Suganami, Tatanka Means, John Malkovich, Ayo Edebiri, and Juliette Lewis attend the premiere of Opus at Eccles Theatre in Park City. (Photo by...

13/03/2025

How Spotify Is Driving Growth, Discovery, and Innovation in the Audiobook Market

Spotify took center stage at the London Book Fair this week, reaffirming our commitment to the audiobook market and showcasing our impact on the publishing indu...

13/03/2025

Spotify Audiobooks Launches a New Publishing Program for Independent Authors

At Spotify, we work every day to lift up new voices, giving creators the opportunity to live off their art. Through Spotify Audiobooks, our in-house publishing ...

13/03/2025

Evolving EO/IR Technology For All-Domain Airborne Law Enforcement

Every time airborne law enforcement (ALE) teams fly, they expect their equipment to perform. Whether airborne units are conducting support for ground teams, bor...

13/03/2025

Craft Interview: Jamie McCombs, Audio Consultant / Sr. Audio

Sunday February 9 saw the annual return of the US' biggest television event, the Super Bowl LIX. Jamie McCombs, Fox Sports Audio Consultant / Sr. Audio capt...

13/03/2025

Craft Interview: Paul Sandweiss, Production Sound Mixer/Audio Director

On Sunday March 2, stars across the film industry gathered at the Dolby Theatre in Los Angeles for the 97th Academy Awards. Production Sound Mixer Paul Sandweis...

13/03/2025

Riedel To Showcase New StageLink Smart Edge Devices At 2025 NAB Show

WUPPERTAL, Germany Riedel Communications will feature its new StageLink family of smart edge devices, Smart Audio and Mixing Engine (SAME) and Virtual Smart Pan...

13/03/2025

TAG Video Systems and Harmonic Partner to Deliver Enhanced Real-Time Monitoring for VOS360 Streaming Workflows at the 2025 NAB Show

TAG Video Systems and Harmonic Partner to Deliver Enhanced Real-Time Monitoring ...

13/03/2025

DigitalGlue Invites NAB Visitors to Experience New Features in Managed Storage Platform that Empowers Video Teams to Scale Effortlessly

DigitalGlue Invites NAB Visitors to Experience New Features in Managed Storage P...

13/03/2025

FOR-A America Theme - Connecting the Present, Building the Future - Comes to Life at NAB 2025 Exhibition

FOR-A America Theme - Connecting the Present, Building the Future - Comes to Lif...

13/03/2025

Ajit Pai Appointed President of CTIA

CTIA, the wireless industry association, has named former FCC Chairman Aji Pai as its President and Chief Executive Officer, effective April 1. He replaces Mere...

13/03/2025

NAB: FCC's 60 Minutes Investigation Is Unconstitutional, Invalid

he National Association of Broadcasters is urging the FCC to end its investigation of that controversial CBS interview with Kamala Harris stating there is no ...

13/03/2025

CBS Miami to Launch AR Coverage of Weather and Sports for March Madness

MIAMI CBS News & Stations continues to expand its use of augmented and virtual reality technologies with the planned launch of an augmented reality/virtual real...

13/03/2025

Meet the co-founder and chief customer success & innovation officer

Srividhya Srinivasan, co-founder and chief customer success & innovation Officer at Amagi, tells TVBEurope how staying ahead of the latest trends is essential f...

13/03/2025

FCC Chairman Carr Launches Massive Deregulation Initiative

WASHINGTON FCC Chairman Brendan Carr announced that the agency has launched a massive, new deregulatory initiative that could potentially subject virtually all ...

13/03/2025

SDVI Integrates Rally With Spectra Vail

SUNNYVALE, Calif. SDVI has announced that it has integrated its Rally media supply chain management platform with the Spectra Vail multi-cloud data management s...

13/03/2025

FCC Approves Gray's Acquisition of KXLT

ATLANTA Gray Media has announced that the Federal Communications Commission (FCC) has granted a waiver of its local ownership rules to permit Gray Media to acqu...

13/03/2025

NAB Show 2025 Exhibitor Insight: Blackmagic Design

TV Tech: What do you anticipate will be the most significant technology trends at the 2025 NAB Show?...

13/03/2025

Watch Student Naomi Soleils Folk Pop Performance on The Voice

Watch Student Naomi Soleils Folk Pop Performance on The Voice The songwriting major sang Stars by Grace Potter and the Nocturnals during the blind auditions. ...

13/03/2025

Roku Debuts NWSL Zone' Within Roku Sports to Spotlight Live Games, Content

Roku Debuts NWSL Zone' Within Roku Sports to Spotlight Live Games, Content Feature marks Rokus first women's league-branded zone within service By Bra...

13/03/2025

Pixels, Images, Video, AI - and Us: A Perspective on AI from NDI Inventor Andrew Cross

Pixels, Images, Video, AI - and Us: A Perspective on AI from NDI Inventor Andrew...

13/03/2025

SVG New Sponsor Spotlight: Lighting Design Group's Steve Brill, Dennis Size on Completing Customizable Studios for All Clients

SVG New Sponsor Spotlight: Lighting Design Group's Steve Brill, Dennis Size ...

13/03/2025

IOC, Comcast NBCU Ink $3B Media-Rights Extension for Olympic Games Through 2036; Add Digital Projects, Initiatives

IOC, Comcast NBCU Ink $3B Media-Rights Extension for Olympic Games Through 2036;...

13/03/2025

NCAA March Madness Live Returns with Expanded Availability of MultiView Vertical Video Feed, Mascot Mode, and Popular Boss Button

NCAA March Madness Live Returns with Expanded Availability of MultiView Vertical...

13/03/2025

SVG Sit-Down: Cosm's Devin Poolman on What It Takes To Deliver the Immersive Experience for Daytona, The PLAYERS, and March Madness

SVG Sit-Down: Cosm's Devin Poolman on What It Takes To Deliver the Immersive...

13/03/2025

Sky Business Launches Cloud Voice A New Cloud Communication Solution for UK Businesses

Sky Business, Sky's B2B division, providing connectivity and content to busi...

13/03/2025

Rohde & Schwarz launches R&S NRP140TWG(N) thermal power sensor: A new benchmark for F band applications

Rohde & Schwarz launches R&S NRP140TWG(N) thermal power sensor: A new benchmark ...

13/03/2025

The ICG Marketing Survey 2025

We asked the questions, analysed the answers and now we're excited to share the results of the fifth edition of the ICG Marketing Survey. Our 2025 survey p...

13/03/2025

Harmonic Amps Up Video Streaming Efficiency with New Origin Capabilities

SAN JOSE, Calif. - March 13, 2025 Harmonic (NASDAQ: HLIT) today announced a breakthrough in video streaming innovation with the launch of new origin capabilitie...

13/03/2025

Haivision Showcases Mission-Critical Video Solutions at SOF Week 2025

Haivision Showcases Mission-Critical Video Solutions at SOF Week 2025 Haivision's video wall systems, ISR technology, and DoDIN APL-certified video distri...

13/03/2025

FOR-A America Theme Connecting the Present, Building the Future Comes to Life at NAB 2025 Exhibition

Company Leads the Way with New Software-Based Production Platform, 12G Switcher,...

13/03/2025

2025-03-13

A new Apple Immersive concert experience, Metallica, is coming to Apple Vision Pro this Friday, March 14. Filmed in Mexico City during the sold-out second-year ...

13/03/2025

Italia 90 Republic of Ireland Squad, Riverdance, Cian Ducrot & B*Witched on Friday's Late Late Show

Here is your host, Patrick Kielty! Shake your Shamrocks, Patrick Kielty will be...

13/03/2025

RT Celebrating all things Irish this St. Patrick's Weekend

This St. Patrick's weekend, RT invites you to celebrate all things Irish, showcasing the very best of Irish sport, entertainment and live coverage from the...

13/03/2025

GTC 2025 - Announcements and Live Updates

What's next in AI is at GTC 2025. Not only the technology, but the people and ideas that are pushing AI forward - creating new opportunities, novel solution...

13/03/2025

T-Mobile, Thales and SIMPL ease IoT deployments with a flexible and secure connectivity solution

Facebook Twitter LinkedIn By combining T-Mobile's robust network, Thal...

13/03/2025

Relive the Magic as GeForce NOW Brings More Blizzard Gaming to the Cloud

Bundle up - GeForce NOW is bringing a flurry of Blizzard titles to its ever-expanding library. Prepare to weather epic gameplay in the cloud, tackling the genr...

13/03/2025

Gaming Goodness: NVIDIA Reveals Latest Neural Rendering and AI Advancements Supercharging Game Development at GDC 2025

AI is leveling up the world's most beloved games, as the latest advancements...

13/03/2025

Drop It Like It's Mod: Breathing New Life Into Classic Games With AI in NVIDIA RTX Remix

PC game modding is massive, with over 5 billion mods downloaded annually. Mods p...

12/03/2025

Como o Impacto Cultural e Financeiro da Indstria Musical Define Seu Sucesso em 2025

O Spotify acaba de lan ar o relat rio Loud & Clear deste ano, uma vis o transpar...

12/03/2025

Cmo el impacto cultural y financiero de la industria musical define su xito en 2025

Spotify acaba de presentar el informe Loud & Clear de este a o, una mirada trans...

12/03/2025

Nourish Mind, Body, and Soul This Ramadan With Spotify

Ramadan, a period of profound spiritual significance for Muslims worldwide, is a time for fasting, prayer, reflection, and community. Enrich your experience thi...

12/03/2025

How the Music Industry's Cultural and Financial Impact Define Its Success in 2025

Spotify has just unveiled this year's Loud & Clear report, a transparent loo...

12/03/2025

FAST now transcends back catalog content

More than 70% of FAST programming has been produced since 2010, according to new Gracenote report NEW YORK March 12, 2025 Gracenote, the content data busin...

12/03/2025

Viamedia Adopts ShowSeeker Pilot To Streamline Ad Workflows

GEONA, Nev. Independent digital and linear advertising rep firm Viamedia will adopt cloud-based ShowSeeker Pilot as its primary ad campaign and order management...

12/03/2025

Mediagenix Appoints Wael Yasin as Sales Director Central Europe

BRUSSELS Mediagenix has announced that Wael Yasin has joined the company as sales director Central Europe....

12/03/2025

Omdia: Global Online Consumer Expenditure to Hit $6.6 Trillion by 2029

LONDON A new study highlights opportunities for shoppable TV and the massive impact online consumer spending is having on the economy, with Omdia predicting tha...

12/03/2025

Comcast Technology Solutions Upgrades to Interra Systems BATON Version 9

CUPERTINO, Calif. Interra Systems has announced that Comcast Technology Solutions has integrated recent updates to BATON Version 9 into its operations....

12/03/2025

Nevion announces new 400G addition to its eMerge SDN media fabric offering

Nevion announces new 400G addition to its eMerge SDN media fabric offering Brie Clayton March 12, 2025 0 Comments High-capacity switch enhances existi...

12/03/2025

DaVinci Resolve Studio Delivers Cinematic Sound for Adam Bol

DaVinci Resolve Studio Delivers Cinematic Sound for Adam Bol Brie Clayton March 12, 2025 0 Comments Feature film relies on DaVinci Resolve Studio for ...