Research Reveals Control Of Potent Immune = Regulator

From: Subject: Research Reveals Control Of Potent Immune Regulator Date: Tue, 23 May 2006 18:48:20 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0014_01C67E99.761017A0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0014_01C67E99.761017A0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://researchnews.osu.edu/archive/ifngnkcell.htm Research Reveals Control Of Potent Immune = Regulator

=20

OSU News = Research=20 Archive Search an archive of past research = stories.=20
Coverage of OSU = Research=20
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(Last updated 5/22/06) =

Previous stories = pertaining to=20 Professor Caligiuri's research:

"Front-Line=20 Immune Cells Mature In Four Stages, Study Shows," 4/19/06.=20

"Scientists=20 Identify New Model Of NK Cell Development," 3/18/05. =

"Genome-Wide = Mouse=20 Study Yields Link To Human Leukemia," 2/22/05.

"New Gene = Alteration=20 Finds Points Tp Agressive Leukemia Treatment," = 1/27/98.

"Possible New=20 Approach To Brian Tumors In AIDS Patients,"=20 10/20/97.

[Embargoed until noon ET Tuesday May 23, 2006, to = coincide with=20 publication in the journal Immunity.]

RESEARCH REVEALS CONTROL OF POTENT IMMUNE REGULATOR

COLUMBUS , Ohio =96 A new study reveals how the production of a = potent=20 immune regulator called interferon gamma = (IFNg)=20 is controlled in natural = killer=20 (NK) cells, immune cells that typically defend the body = against cancer=20 and infections.

Michael=20 Caligiuri

IFNg, produced by NK cells and other cell types, plays a = critical role=20 in killing pathogen-infected cells and in defending against tumor = cells.=20 However, overproduction of IFNg is also dangerous to the body and = can=20 cause autoimmune diseases. But exactly how the body tightly = controls IFNg=20 production =96 and, therefore, NK-cell activity =96 is not known. =

The study, published in the May issue of the journal Immunity, looked at = substances called pro-inflammatory cytokines, which cause NK cells = to make=20 IFNg and stimulate their activity. It also looked at transforming = growth=20 factor beta (TGFb), a substance also made by NK cells that lowers = IFNg=20 production.

The research, by investigators with the Ohio = State=20 University Comprehensive Cancer Center =96 Arthur G. James Cancer Hospital = and=20 Richard J. Solove Research Institute, found that the = pro-inflammatory=20 cytokines not only cause NK cells to make IFNg, but they also shut = down=20 TGFb signaling, which inhibits production of IFNg.

That is, the cytokines not only increase some positive = regulators of=20 IFNg production, but they also shut down the TGFb signals that = inhibit=20 IFNg production.

In addition, the scientists found that TGFb turns down IFNg = production=20 =96 and, therefore, NK cell activity =96 both directly and = indirectly.

=93In each = instance, these=20 regulatory cytokines deliver a double whammy,=94 Caligiuri = says. =93They=20 turn on what is needed and turn off anything that interferes = with=20 it.=94

The direct mechanism turns off the IFNg gene itself. The = indirectly=20 mechanism blocks a protein that normally turns up IFNg production. =

=93Our findings provide important details about the fine = balance between=20 positive and negative regulators of IFNg production in NK = cells,=94 says=20 principal investigator Michael = A.=20 Caligiuri, director of the OSU Comprehensive Cancer Center. = =93Mother=20 Nature uses a symphony of cytokines that result in exquisitely = tight=20 control of its production in the healthy state.

=93This might help us harness the cancer-killing ability of NK = cells to=20 control tumor growth and lead to new treatments that complement = current=20 cancer therapy,=94 he says.

The body carefully regulates IFNg levels. If there is too = little of the=20 substance, the risk of infection and cancer rises. If there is too = much=20 IFNg, NK cells become too plentiful and autoimmune diseases such = as=20 inflammatory bowel disease can occur.

=93Our findings explain the yin and yang of the system that = controls NK=20 cells,=94 says first author Jianhua Yu, a post-doctoral student in = Caligiuri's laboratory. =93When NK cells are called into action, = the body=20 not only turns up the activation pathway, it also shuts down the=20 anti-activation pathway.=94

Likewise, when TGFb turns down NK cell activity, it not only = turns off=20 the IFNg gene, it also shuts down the pathway that activates the = gene.=20

=93In each instance, these regulatory cytokines deliver a = double whammy,=94=20 Caligiuri says. =93They turn on what is needed and turn off = anything that=20 interferes with it.=94

Funding from the National = Cancer=20 Institute supported this research.

Contact: Darrell E. Ward, Medical Center=20 Communications, 614-293-3737, or Darrell.Ward@osumc.edu

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