Essential Role of CCR6 in Directing Activated T Cells to the Skin during Contact Hypersensitivity

The nfkb2 gene encodes the p100 precursor which produces the p52 protein after proteolytic cleavage of its COOH-terminal domain. Although the p52 product can act as an alternative subunit of NF-κB, the p100 precursor is believed to function as an inhibitor of Rel/NF-κB activity by cytoplasmic retention of Rel/NF-κB complexes, like other members of the IκB family. However, the physiological relevance of the p100 precursor as an IκB molecule has not been understood. To assess the role of the precursor in vivo, we generated, by gene targeting, mice lacking p100 but still containing a functional p52 protein. Mice with a homozygous deletion of the COOH-terminal ankyrin repeats of NF-κB2 (p100−/−) had marked gastric hyperplasia, resulting in early postnatal death. p100−/− animals also presented histopathological alterations of hematopoietic tissues, enlarged lymph nodes, increased lymphocyte proliferation in response to several stimuli, and enhanced cytokine production in activated T cells. Dramatic induction of nuclear κB–binding activity composed of p52-containing complexes was found in all tissues examined and also in stimulated lymphocytes. Thus, the p100 precursor is essential for the proper regulation of p52-containing Rel/NF-κB complexes in various cell types and its absence cannot be efficiently compensated for by other IκB proteins.

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Functional heterogeneity of CD4+ T cells in liver inflammation

Seminars in Immunopathology ◽

10.1007/s00281-021-00881-w ◽

2021 ◽

Author(s):

Franziska Muscate ◽

Anna Woestemeier ◽

Nicola Gagliani

Keyword(s):

T Cells ◽

Essential Role ◽

Inflammatory Diseases ◽

Cell Polarization ◽

Maturation Stage ◽

Liver Inflammation ◽

Functional Heterogeneity ◽

Immune Mediated ◽

T Cell Polarization

AbstractCD4+ T cells play an essential role in orchestrating adequate immunity, but their overactivity has been associated with the development of immune-mediated inflammatory diseases, including liver inflammatory diseases. These cells can be subclassified according to their maturation stage, cytokine profile, and pro or anti-inflammatory functions, i.e., functional heterogeneity. In this review, we summarize what has been discovered so far regarding the role of the different CD4+ T cell polarization states in the progression of two prominent and still different liver inflammatory diseases: non-alcoholic steatohepatitis (NASH) and autoimmune hepatitis (AIH). Finally, the potential of CD4+ T cells as a therapeutic target in both NASH and AIH is discussed.

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SHP-1 Acts as a Key Regulator of Alloresponses by Modulating LFA-1-Mediated Adhesion in Primary Murine T Cells

Molecular and Cellular Biology ◽

10.1128/mcb.00294-16 ◽

2016 ◽

Vol 36 (24) ◽

pp. 3113-3127 ◽

Cited By ~ 3

Author(s):

Martin G. Sauer ◽

Jessica Herbst ◽

Ulf Diekmann ◽

Christopher E. Rudd ◽

Christian Kardinal

Keyword(s):

T Cells ◽

T Cell ◽

Tyrosine Phosphatase ◽

Activated T Cells ◽

Sirna Knockdown ◽

Antigen Presenting ◽

Pharmaceutical Agents ◽

Interfering Rna ◽

Clinical Potential

The clinical potential of transplantation is often reduced by T cell-mediated alloresponses that cause graft rejection or graft-versus-host disease. Integrin-mediated adhesion between alloreactive T cells and antigen-presenting cells is essential for allorejection. The identity of the signaling events needed for the activation of integrins such as LFA-1 is poorly understood. Here, we identified a novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine LFA-1-mediated adhesion in an allograft setting. Upon alloactivation, SHP-1 activity is reduced, resulting in an increase in LFA-1 adhesion compared to that for syngeneically activated T cells. The importance of these differential activation properties was further indicated by small interfering RNA (siRNA) knockdown of SHP-1 in syngeneically and allogeneically stimulated T cells. Mechanistically, SHP-1 modulated the binding of SLP-76 to ADAP by dephosphorylation of the YDGI tyrosine motif of ADAP, a known docking site for the Src family kinase Fyn. This novel key role of SHP-1 in the regulation of LFA-1-mediated adhesion may provide a new insight into T cell-mediated alloresponses and may pave the way to the development of new immunosuppressive pharmaceutical agents.

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Regulation of expression of the IL-2 and IL-5 genes and the role of proteins related to nuclear factor of activated T cells

Journal of Allergy and Clinical Immunology ◽

10.1016/s0091-6749(95)70197-4 ◽

1995 ◽

Vol 96 (6) ◽

pp. 1126-1135 ◽

Cited By ~ 12

Author(s):

L TSURUTA ◽

H LEE ◽

E MASUDA ◽

T YOKOTA ◽

N ARAI ◽

...

Keyword(s):

T Cells ◽

Nuclear Factor ◽

Regulation Of Expression ◽

Activated T Cells

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Cytokines and Adhesion Molecules in Allergic Rhinitis

American Journal of Rhinology ◽

10.2500/105065898782103007 ◽

1998 ◽

Vol 12 (1) ◽

pp. 3-8 ◽

Cited By ~ 21

Author(s):

Claus Bachert ◽

Martin Wagenmann ◽

Gabriele Holtappels

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Adhesion Molecules ◽

Current Knowledge ◽

Allergic Inflammation ◽

Allergen Challenge ◽

Activated T Cells ◽

Viral Rhinitis

This review summarizes our current knowledge of nasal allergic inflammation based on studies of cytokines, chemokines, and adhesion molecules in allergic rhinitis. The article also includes some aspects of viral rhinitis. Due to artificial or natural allergen exposure, an increase in the number of eosinophils and basophils, mast cells, IgE-positive cells, macrophages, monocyte-like cells, Langerhans cells, and activated T-cells can be observed within the mucosa and on the mucosal surface. Mediators are known to be released in response to allergens, but do not seem to be adequate to initiate the cell recruitment. After antigen challenge, the release of proinflammatory and regulatory cytokines could be demonstrated, and TH2-type cytokine mRNA upregulation in allergic mucosa has been shown. Proinflammatory cytokines initiate an adhesion cascade and activate T-cells that create an “atopic” cytokine environment within the tissue, which also may be linked to the long-term selective recruitment of eosinophils. However, the acute selective migration of eosinophils after allergen challenge is not fully understood, nor is the role of chemokines in allergic and viral rhinitis. Allergic rhinitis clearly represents an inflammatory reaction.

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