Autoimmune rheumatologic diseases

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Autophagic Memory in Stress Experienced Human T Cells

Thursday, June 15
5:45 PM - 7:00 PM

Autophagy is required for memory T cell generation and maintenance. Previous studies from our group showed higher levels of autophagy in CD4+ T cells from RA patients. Here, we hypothesise that T cells which experience immunological encounters and activation attain, when compared to naive cells, heightened autophagic levels when a similar stimulus is encountered again, a phenomenon, which we term "autophagic memory". This phenomenon may be pathogenically relevant. Flow cytometry analysis of T cells from healthy individual showed indeed higher autophagy levels in memory CD4 and CD8 cells after activation, compared to naive T cells. However the basal level of autophagy was similar in both cell types, suggesting a memory for autophagy. To dissect the molecular mechanisms of autophagic memory, we trained human T cells in low serum medium, to elicit stress-induced activation, for 5 days. The cells were then cultured in 10% serum media for 100 generations. RNA-sequencing and methylome analysis of the trained and control cells at 5, 30,70 and 100 generations, identified clusters of genes stably up or down regulated in trained cells compared to control cells until the 30th generations, suggesting for role of these genes in retention of memory for autophagy.


In conclusion, we describe here epigenetic and trasciptional elements which determine and control persistence of autophagic memory in experienced T cells. We suggest that autophagic memory is an integral part of efficient activation of memory T cells, and it also contributes to persistence of T cell mediated inflammation in autoimmunity.

Pavanish Kumar

Research fellow
SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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    Jorg Van Loosdregt

    Research Fellow
    SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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      Suzan Saidin

      SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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        Bhairav Paleja

        Research Fellow
        SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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          Salvatore Albani

          Director
          SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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