Immune Regulation News Volume 5.12 | Apr 5 2013

Human CD1c⁺ Dendritic Cells Drive the Differentiation of CD103⁺ CD8⁺ Mucosal Effector T Cells via the Cytokine TGF-ß
Investigators analyzed, by using lung tissues from humans and humanized mice, the role of human CD1c⁺ and CD141⁺ dendritic cells (DCs) in determining the type of CD8⁺ T cell immunity generated to live-attenuated influenza virus vaccine. They found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8⁺ T cells in vitro. [Immunity] Abstract

Hunger-Promoting Hypothalamic Neurons Modulate Effector and Regulatory T-Cell Responses
The authors showed that selective knockdown of Sirtuin 1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4⁺ T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. [Proc Natl Acad Sci USA] Abstract

Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-versus-Host Disease
The authors recently reported that daily administration of low-dose interleukin-2 (IL-2) induces selective expansion of functional T regulatory cells and clinical improvement of chronic graft-versus-host disease. To define the mechanisms of action of IL-2 therapy, they examined the immunologic effects of this treatment on homeostasis of CD4⁺ T cell subsets after transplant. [Sci Trans Med] Abstract

Cutting Edge: A Novel, Human-Specific Interacting Protein Couples FOXP3 to a Chromatin-Remodeling Complex that Contains KAP1/TRIM28
Researchers identified and characterized a human-specific FOXP3-interacting protein, referred to as FIK (FOXP3-interacting KRAB domain-containing protein). FIK is highly expressed in regulatory T cells (Tregs) and acts as a bridging molecule to link FOXP3 with the chromatin-remodeling scaffold protein KAP1 (TIF-1ß/TRIM28). Disruption of the FOXP3-FIK-KAP1 complex in Tregs restored expression of FOXP3-target genes and abrogated the suppressor activity of the Tregs. [J Immunol] Abstract

Restoring Immune Function of Tumor-Specific CD4⁺ T Cells during Recurrence of Melanoma
Scientists developed a mouse melanoma model in which initial regression of advanced disease was followed by tumor recurrence. During recurrence, Foxp3⁺ tumor-specific CD4⁺ T cells became PD-1⁺ and represented more than 60% of the tumor-specific CD4⁺ T cells in the host. [J Immunol] Abstract

Enrichment of Regulatory T Cells in Invasive Breast Tumor Correlates with the Upregulation of IL-17A Expression and Invasiveness of the Tumor
Investigators showed that CD25⁺CD4⁺ T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4 and CD103, indicating that tumor-infiltrating regulatory T cells are functional and possibly recruited by CCL22. Additionally, they observed upregulation of Th17-related molecules (IL-17A, RORC and CCR6) and IL-17A produced by tumor-infiltrating CD4⁺ and CD8⁺ T lymphocytes. [Eur J Immunol] Abstract

CD4⁺ T Cells Develop Anti-Retroviral Cytotoxic Activity in the Absence of Regulatory T Cells and CD8⁺ T Cells
Researchers took advantage of a transgenic mouse in which regulatory T cells can be selectively depleted to determine the influence of such cells on retrovirus-specific CD4⁺ T cell responses during an ongoing infection. [J Virol] Abstract

Macrophages as IL-25/IL-33-Responsive Cells Play an Important Role in the Induction of Type 2 Immunity
The authors demonstrated that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. [PLoS One] Full Article

IFNß Autocrine Feedback Is Required to Sustain TLR Induced Production of MCP-1 in Macrophages
Chemokines, including MCP-1, are crucial to mounting an effective immune response due to their ability to recruit other immune cells. The authors showed that sustained LPS or poly(I:C)-stimulated MCP-1 production requires an IFNß-mediated feedback loop. [FEBS Lett] Abstract

BATF Regulates the Development and Function of IL-17 Producing iNKT Cells
Tg mice overexpressing BATF in T cells were used together with Batf null mice to investigate how altering levels of BATF expression in T cells impacts the development and function of a recently characterized population of iNKT cells expressing IL-17. [BMC Immunol] Abstract | Full Article

The Dendritic Cell Lineage: Ontogeny and Function of Dendritic Cells and Their Subsets in the Steady State and the Inflamed Setting
This review discusses major advances in the understanding of the regulation of dendritic cell lineage commitment, differentiation, diversification, and function in situ. [Annu Rev Immunol] Abstract

T Cell Receptor Signaling Networks: Branched, Diversified and Bounded
Several recent publications have provided important insights into how dysregulation of T cell signaling and the development of autoreactivity can result if the branching and integration of signaling pathways are perturbed. This review discusses how these findings highlight the importance of spatial segregation of individual signaling components as a way of regulating T cell responsiveness and immune tolerance. [Nat Rev Immunol] Abstract

Interaction between Natural Killer Cells and Regulatory T Cells: Perspectives for Immunotherapy
The authors discuss the recent information on the interaction between regulatory T (Treg) cells and natural killer cells under healthy and pathologic conditions, to describe the specific conditions in which this interaction takes place, the effect of Treg cells on hematopoietic stem cell differentiation and the consequences of this interaction on the optimization of immunotherapeutic protocols. [Cel Mol Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.

Lupus LA Founder Dr. Daniel Wallace Joining with Another Lupus Specialist to Expand Research Program
Dr. Daniel Wallace, founder of Lupus Research Institute Coalition member Lupus LA and Dr. Swamy Venuturupalli are joining together to broaden their autoimmune disease research program. The two noted clinician scientists will base an aggressive and well-funded study program out of “The Wallace Rheumatic Diseases Research Center” in West Hollywood, CA. [Lupus Research Institute] Press Release

Sanofi and Transgene Announce Innovative Long-Term Collaboration for the Production of Immunotherapy Treatments
Sanofi and Transgene SA announced a collaboration agreement for the creation of a new state-of-the-art industrial platform dedicated to the production of immunotherapy products including Transgene’s therapeutic products. [Sanofi] Press Release

Grant: Cooperative Centers on Human Immunology (U19) (RFA-AI-13-016)
The purpose of this Funding Opportunity is to support hypothesis-testing, mechanistic studies on the activation and regulation of human immune responses in the context of infectious disease. This research program was initiated by National Institute of Allergy and Infectious Diseases in fiscal year 2003 and is being renewed for the second time through open competition. [National Institutes of Health, United States] Link

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