POU2AF1(+) follicular helper T (Tfh) cells in obstructive sleep apnea syndrome (OSAS) (69.3)

Abstract OSAS is attributable to periodic collapse of the upper airway due to adenotonsillar hypertrophy, featuring prominent germinal centers and wide interfollicular zones. However, the mechanism is still unclear. Here we present the possible involvement of Tfh cells in the pathogenesis of OSAS as indicated by comprehensive analysis of tonsillar lymphocytes of OSAS patients. The results revealed that tonsillar Tfh cells were plentiful in OSAS compared to recurrent tonsillitis (RT) without any discrepancy of T-cell components between the tonsils of OSAS and RT patients, indicating a ‘Tfh shift’ in OSAS tonsils. In addition, in vitro experiments delineated a unique function of the Tfh cells of OSAS, which could help expand the number of naive B cells and, more extensively, memory B cells, which allowed the Tfh cells to produce larger amounts of IL-4 and IFN-γ. Microarray studies newly identified transcripts characterizing the Tfh cells, including TIGIT and POU2AF1 regulating CXCR5 of B cells. Indeed, B-cell expansion was under the control of TIGIT, and large numbers of POU2AF1(+) Tfh cells were observed in and outside of germinal centers of OSAS tonsils. Overall these findings indicate that POU2AF1(+) Tfh cells cooperate with regional B-cell subsets to induce lymphoid hyperplasia.Focusing on the TIGIT-selective regulation of POU2AF1(+) Tfh cells, further investigations may provide a new modality for a noninvasive approach to treatment of this condition.