NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-γ and CXCR3 chemokines

Abstract

Ischemia-reperfusion injury (IRI) triggers an inflammatory cascade that is initiated

Proinflammatory Environment Dictates the IL-17–Producing Capacity of Human Invariant NKT Cells

“…More physiological Ags for iNKT cells have been identified, including bacterial glycolipids such as a-galacturonosylceramide, a-glucuronosylceramide, and agalactosyl-diacylglycerol, and mammalian glycolipids such as isoglobotrihexosylceramide, disialoganglioside GD3, and charged glycosphingolipids (5-10). After Ag stimulation, iNKT cells promptly produce a variety of cytokines enabling them to modulate the immune response in many diseases, including cancer, autoimmunity, infection, and allergy (1,2,(10)(11)(12)(13)(14)(15)(16)(17)(18). It remains unclear how this particular T cell population can exert such wide and contrasting effects despite their limited TCR repertoire.…”

Advances in Sickle Cell Therapies in the Hydroxyurea Era

“…Integral to these cellular interactions are inflammatory mediators, which activate endothelial cells, leukocytes and platelets and attract additional leukocytes to the site of occlusion (20). After the resolution of the microvascular occlusion, ischemiareperfusion injury may further amplify inflammation, creating a vicious cycle that sustains and propagates vasoocclusion (21,22). New therapeutic targets have emerged as understanding of vaso-occlusion has progressed beyond the simple concept of a "log jam" of sickled erythrocytes in small vessels.…”

“…In addition, interferon-γ stimulates the production of the chemokines C-X-C motif chemokine 9 precursor (CXCL9), CXCL10 and CXCL11, potent chemoattractants for CXC receptor 3 (CXCR3)-expressing lymphocytes (36). In a mouse model of SCD, interruption of iNKT cell activation or depletion of iNKT cells reduces tissue injury (22).…”

“…Administration of an adenosine A 2A receptor agonist is one strategy used to block iNKT cell activation in a SCD mouse model (22,37). On the basis of that preclinical data, a phase I study of the A 2A receptor agonist, regadenoson, was performed in patients (38).…”

MicroRNAs are key regulators controlling iNKT and regulatory T-cell development and function

“…Upon antigenic stimulation, iNKT cells rapidly and robustly produce a broad range of cytokines, which allow them to modulate the function of variety of other immune cells, including dendritic cells, Th17 and Th1 T cells, and to regulate both innate and adaptive immune responses. [44][45][46][47] In addition, iNKT cells can secrete perforin, granzymes and FasL when activated and mediate protective immune functions, including tumor rejection and protection against infectious microbes. [48][49][50] Defective iNKT development and/or inappropriate iNKT activation and function are associated with a broad spectrum of diseases, ranging from autoimmunity, cancer, infection and allergies to allograft rejection.…”