Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet

Autor: Nus, M, Sage, AP, Lu, Y, Masters, L, Lam, BYH, Newland, S, Weller, S, Tsiantoulas, D, Raffort, J, Marcus, D, Finigan, A, Kitt, L, Figg, N, Schirmbeck, R, Kneilling, M, Yeo, GSH, Binder, CJ, de la Pompa, JL, Mallat, Z
Přispěvatelé: Nus Chimeno, Meritxell [0000-0002-6378-8910], Sage, Andrew [0000-0001-7255-3497], Lu, Yuning [0000-0001-8619-9724], Lam, Brian [0000-0002-3638-9025], Yeo, Giles [0000-0001-8823-3615], Mallat, Ziad [0000-0003-0443-7878], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
DOI: 10.17863/cam.13793
Popis: Splenic marginal zone B (MZB) cells, positioned at the interface between circulating blood and lymphoid tissue, detect and respond to blood-borne antigens. Here we show that MZB cells in mice activate a homeostatic program in response to a high-cholesterol diet (HCD) and regulate both the differentiation and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in an ATF3-dependent manner and increased the interaction between MZB cells and pre-TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration of TFH cell differentiation, reduced TFH abundance and suppression of the proatherogenic TFH response. Our findings reveal a previously unsuspected role for MZB cells in controlling the TFH–germinal center response to a cholesterol-rich diet and uncover a PDL1-dependent mechanism through which MZB cells use their innate immune properties to limit an exaggerated adaptive immune response.
Databáze: OpenAIRE