Byeongho Jung, Gerardo Ferrer, Pui Yan Chiu, Rukhsana Aslam, Anita Ng, Florencia Palacios, Michael Wysota, Martina Cardillo, Jonathan E Kolitz, Steven L Allen, Jacqueline C Barrientos, Kanti R Rai, Nicholas Chiorazzi, Barbara Sherry
Chronic lymphocytic leukemia (CLL) results from expansion of a CD5+ B-cell clone that requires interactions with other cell types, including T cells. Moreover, CLL patients have elevated circulating IL17A+ and IL17F+ CD4+ T cells (Th17s), with higher IL17A+Th17s correlating with better outcomes. We report that CLL Th17s express more miR155, a Th17 differentiation regulator, than control Th17s, despite naïve CD4+ T cell (TN) basal miR155 levels being similar in both. We also found that CLL cells directly regulate miR155 levels in TN, thereby affecting Th17 differentiation by documenting that: co-culturing TN with resting (Brest) or activated (Bact) CLL cells alters the magnitude and direction of T-cell miR155 levels; CLL Bact promote IL17A+ and IL17F+ T cell generation by a miR155-dependent mechanism, confirmed by miR155 inhibition; co-cultures of TN with CLL Bact lead to a linear correlation between the degree and direction of T-cell miR155 expression changes and IL17F production, but not IL17A; Bact-mediated changes in TN miR155 expression correlate with outcome, irrespective of IGHV mutation status, a strong prognostic indicator...
May 5, 2022: JCI Insight