Volume 11 Issue 1, January 2010

Just as removing one or two poorly chosen blocks can reduce a neat but precariously balanced stack to a pile of rubble, mutating or impairing one or a few mechanisms responsible for maintaining immune tolerance can precipitate an autoimmune attack. The series of articles in this Focus issue cover what is known about the biological processes that underpin immune tolerance and highlight the possibility that the limited understanding of the etitology and pathogenesis of autoimmune diseases may indicate that additional important immune tolerance mechanisms still await identification. Artwork by Lewis Long.

Editorial

Lighting the way forward

Although recent progress has aided our understanding of the processes that prevent immune tolerance breakdown, this Focus issue illustrates how much remains unknown about susceptibility to and pathogenesis of autoimmune diseases.

Editorial 01 Jan 2010

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Overview

Levees of immunological tolerance

Diane Mathis
Christophe Benoist
Overview 17 Dec 2009

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Review Article

Regulatory T cells exert checks and balances on self tolerance and autoimmunity

Kajsa Wing
Shimon Sakaguchi
Review Article 17 Dec 2009
Checkpoints in lymphocyte development and autoimmune disease

Harald von Boehmer
Fritz Melchers
Review Article 17 Dec 2009
Mechanisms maintaining peripheral tolerance

Daniel L Mueller
Review Article 17 Dec 2009
Influence of microbial environment on autoimmunity

Alexander V Chervonsky
Review Article 17 Dec 2009

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Perspective

Autoimmunity: increasing suspects in the CD4⁺ T cell lineup

Matthew T Palmer
Casey T Weaver
Perspective 17 Dec 2009
Mixed results with modulation of T_H-17 cells in human autoimmune diseases

Lawrence Steinman
Perspective 17 Dec 2009

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Research Highlights

Research Highlights

Research Highlights 01 Jan 2010

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News & Views

Glimpsing the real CD4⁺ T cell response

The present views of how CD4⁺ T cells respond to antigen are based largely on artificial systems. A highly sensitive approach that allows normal T cell responses to be monitored in physiological conditions overturns some existing ideas about the differentiation of CD4⁺ T cells.

Charles D Surh
Jonathan Sprent
News & Views 01 Jan 2010
Defensins keep the peace too

The mammalian intestine contains a large number of commensal bacterial strains. New work suggests that antimicrobial peptides used for defense against pathogenic bacteria are also used to adjust the balance among bacterial populations and to control intestinal homeostasis.

Alfredo Menendez
Rosana B R Ferreira
B Brett Finlay
News & Views 01 Jan 2010
Taking T cells beyond the diffraction limit

Recent advances in microscopy have enabled imaging of cell surface receptors at ever higher resolutions. A report using the latest technology now provides evidence that the T cell antigen receptor and the adaptor Lat are confined to small islands, which cluster together after triggering of the T cell antigen receptor.

P Anton van der Merwe
Paul D Dunne
Simon J Davis
News & Views 01 Jan 2010

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Research Highlights

Research Highlights

Research Highlights 01 Jan 2010

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Obituary

Eli Sercarz 1934–2009

Irun R Cohen
Obituary 01 Jan 2010

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Article

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

Autophagy facilitates host defense against invading bacteria. Philpott and colleagues show that Nod1 and Nod2 link pathogen sensing to autophagy by recruiting the autophagy protein AGT16L1 to the site of pathogen entry.

Leonardo H Travassos
Leticia A M Carneiro
Dana J Philpott
Article 08 Nov 2009
Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production

Production of mature interleukin 1β (IL-1β) requires Il1b transcription and inflammasome-mediated processing of IL-1β protein. Ruland and colleagues show that the RNA virus sensor RIG-I signals via the adaptors CARD9 and Asc to facilitate both processes.

Hendrik Poeck
Michael Bscheider
Jürgen Ruland
Article 15 Nov 2009
Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines

TLR4 signals via MyD88 and TRIF to activate proinflammatory cytokine and type I interferon responses. Karin and colleagues show that different ubiquitination of TRAF3 via K48 or K63 dictates the ensuing immune response.

Ping-Hui Tseng
Atsushi Matsuzawa
Michael Karin
Article 08 Nov 2009
Enteric defensins are essential regulators of intestinal microbial ecology

Defensins combat pathogenic bacteria invading the mammalian intestine. Salzman and co-workers find that defensins influence the composition of the small intestinal commensal microbiota and the presence of interleukin 17–producing T cells in the lamina propria.

Nita H Salzman
Kuiechun Hung
Nicolaas A Bos
Article 22 Oct 2009
Different routes of bacterial infection induce long-lived T_H1 memory cells and short-lived T_H17 cells

Naive CD4⁺ T cells can differentiate into distinct polarized effector cells, but detailed characterization of physiologic CD4 memory is lacking. Jenkins and colleagues show that T_H1 and T_H17 memory cells differ in longevity and arise via different infection routes.

Marion Pepper
Jonathan L Linehan
Marc K Jenkins
Article 22 Nov 2009
TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation

TCR movement in the T cell plasma membrane is not well understood. Using three different types of microscopy, Davis and co-workers identify separate islands of Lat and TCR molecules that concatenate after T cell activation.

Björn F Lillemeier
Manuel A Mörtelmaier
Mark M Davis
Article 13 Dec 2009

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Corrigendum

Correction: Corrigendum: Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

Andy L Johnson
L Aravind
Ronald H Schwartz
Corrigendum 01 Jan 2010
Correction: Corrigendum: Thymic self-reactivity selects natural interleukin 17–producing T cells that can regulate peripheral inflammation

Benjamin R Marks
Heba N Nowyhed
Joe Craft
Corrigendum 01 Jan 2010
Correction: Corrigendum: Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE

Mauricio F Farez
Francisco J Quintana
Howard L Weiner
Corrigendum 01 Jan 2010

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Erratum

Erratum: Themis, a T cell–specific protein important for late thymocyte development

Renaud Lesourne
Shoji Uehara
Paul E Love
Erratum 01 Jan 2010

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Focus

Tolerance Breakdown

An overview, four review articles and two perspective articles cover the cellular and molecular mechanisms required to maintain self tolerance, as well as events that can precipitate tolerance breakdown and lead to autoimmunity.

Focus 01 Jan 2010

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Volume 11 Issue 1, January 2010

Editorial

Lighting the way forward

Overview

Levees of immunological tolerance

Review Article

Regulatory T cells exert checks and balances on self tolerance and autoimmunity

Checkpoints in lymphocyte development and autoimmune disease

Mechanisms maintaining peripheral tolerance

Influence of microbial environment on autoimmunity

Perspective

Autoimmunity: increasing suspects in the CD4⁺ T cell lineup

Mixed results with modulation of T_H-17 cells in human autoimmune diseases

Research Highlights

Research Highlights

News & Views

Glimpsing the real CD4⁺ T cell response

Defensins keep the peace too

Taking T cells beyond the diffraction limit

Research Highlights

Research Highlights

Obituary

Eli Sercarz 1934–2009

Article

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production

Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines

Enteric defensins are essential regulators of intestinal microbial ecology

Different routes of bacterial infection induce long-lived T_H1 memory cells and short-lived T_H17 cells

TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation

Corrigendum

Correction: Corrigendum: Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection

Correction: Corrigendum: Thymic self-reactivity selects natural interleukin 17–producing T cells that can regulate peripheral inflammation

Correction: Corrigendum: Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE

Erratum

Erratum: Themis, a T cell–specific protein important for late thymocyte development

Focus

Tolerance Breakdown

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