Ritika Khandpur

Publications (2)11.58 Total impact

• Article: Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis.

  Andrew M Lin, Cory J Rubin, Ritika Khandpur, Jennifer Y Wang, MaryBeth Riblett, Srilakshmi Yalavarthi, Eneida C Villanueva, Parth Shah, Mariana J Kaplan, Allen T Bruce
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  ABSTRACT: IL-17 and IL-23 are known to be absolutely central to psoriasis pathogenesis because drugs targeting either cytokine are highly effective treatments for this disease. The efficacy of these drugs has been attributed to blocking the function of IL-17-producing T cells and their IL-23-induced expansion. However, we demonstrate that mast cells and neutrophils, not T cells, are the predominant cell types that contain IL-17 in human skin. IL-17(+) mast cells and neutrophils are found at higher densities than IL-17(+) T cells in psoriasis lesions and frequently release IL-17 in the process of forming specialized structures called extracellular traps. Furthermore, we find that IL-23 and IL-1β can induce mast cell extracellular trap formation and degranulation of human mast cells. Release of IL-17 from innate immune cells may be central to the pathogenesis of psoriasis, representing a fundamental mechanism by which the IL-23-IL-17 axis mediates host defense and autoimmunity.
  The Journal of Immunology 07/2011; 187(1):490-500. · 5.79 Impact Factor
• Source

  Available from: Andrew M Lin

  Article: Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.

  Eneida Villanueva, Srilakshmi Yalavarthi, Celine C Berthier, Jeffrey B Hodgin, Ritika Khandpur, Andrew M Lin, Cory J Rubin, Wenpu Zhao, Stephen H Olsen, Matthew Klinker, David Shealy, Michael F Denny, Joel Plumas, Laurence Chaperot, Matthias Kretzler, Allen T Bruce, Mariana J Kaplan
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  ABSTRACT: An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.
  The Journal of Immunology 07/2011; 187(1):538-52. · 5.79 Impact Factor