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NKT cell self-reactivity:evolutionary master key of immune homeostasis?

分子细胞生物学报:英文版 2012年第2期4卷 70-78页

作者： shohreh issazadeh-navikas Neuroinflammation Unit Biotech Research and Innovation Centre(BRIC)University of CopenhagenCopenhagen BiocentreOle Maaløes Vej 5DK-2200 Copenhagen NDenmark

Complex immune responses have evolved to protect multicellular organisms against the invasion of *** has exerted strong developmental pressure for specialized functions that can also limit damage to *** arms of immunity,the innate and adaptive immune systems,have evolved for quick,non-specific immune responses to pathogens and more efficient,long-lasting ones upon specific recognition of recurrent *** cells have arisen as the sentinels of these functions,including macrophages,natural killer(NK),and T and ***,a population of immune cells that can exert both of these complex functions,NKT cells,not only share common functions but also exhibit shared cell surface markers of cells of both arms of the immune *** features,in combination with sophisticated maintenance of immune homeostasis,will be *** recent finding of self-peptide reactivity of NKT cells in the context of CD1d,with capacity to regulate multiple auto-immune and inflammatory conditions,motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T *** parallel selection through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T *** views on how self-reactive NKT cells secure such a central role will also be proposed.

关键词： CD1 T regulatory cells autoimmunity cancer programmed death ligand-1

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ADAM12 is a costimulatory molecule that determines Th1 cell fate and mediates tissue inflammation

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Cellular & Molecular Immunology 2021年第8期18卷 1904-1919页

作者： Yawei Liu Robert Bockermann Mahdieh Hadi Iman Safari Belinda Carrion Marie Kveiborg shohreh issazadeh-navikas Neuroinflammation Unit Biotech Research&Innovation Centre(BRIC)Faculty of Health and Medical SciencesUniversity of CopenhagenOle Maaløes Vej 5DK-2200Copenhagen NDenmark BRIC Faculty of Health and Medical SciencesUniversity of CopenhagenOle Maaløes Vej 5DK-2200Copenhagen NDenmark

A disintegrin and metalloproteinase(ADAM)12 was previously found to be expressed in T cells in the inflamed ***,the function of ADAM12 in T-cell responses in general and in tissue inflammation has not been ***,we studied the role of ADAM12 in T-cell responses,fate determination on activation,and its functions in T cells to mediate tissue *** identified ADAM12 as a costimulatory molecule that is expressed on naive T cells and downregulated on ***12 mimics CD28 costimulatory signaling to activate and induce the proliferation of T-helper 1(Th1)*** ADAM12 Fab antibodies trigger T-cell activation by amplifying TCR signaling to stimulate T-bet-mediated IFNγ*** of genomic ADAM12 and its knockdown in T cells diminished T-bet and IFNγproduction in Th1 cells,whereas other T cells,including Th17 cells,were ***12 had similar functions in vivo on myelin antigen(MOG_(35-55))-induced T-cell *** found that genetic loss of ADAM12 profoundly alleviated Th1-mediated neuroinflammation and thus disease severity in experimental autoimmune encephalomyelitis,a model of multiple *** profiling of MOG_(35-55)-specific ADAM12^(−/−)T cells revealed differentially expressed genes that are important for T-cell activation,proliferation,and costimulatory signaling and Th1 pathogenicity,consistent with their inability to cause T-cell-mediated skin inflammation in a model of adoptive delayed-type *** conclude that ADAM12 is a T-cell costimulatory molecule that contributes to the pathogenesis of tissue inflammation and a potential target for the treatment of Th1-mediated diseases.

关键词： T cells T-bet Th17 EAE DTH GM-CSF

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