Follicular Helper T (TFH) Cell Targeting by TLR8 Signaling For Improving HBsAg-Specific B Cell Response In Chronic Hepatitis B Patients

• DOI: 10.3389/fimmu.2021.735913
• Publication Date: 2021-08-27T20:52:46Z
• Authors: Natarajan Ayithan; Lydia Tang; Susanna K. Tan; Diana Chen; Jeffrey J. Wallin; Simon P. Fletcher; Shyam Kottilil; Bhawna Poonia
• Keywords: ELISPOT

Identifying signaling pathways that induce B cell response can aid functional cure strategies for chronic hepatitis infection (CHB). TLR8 activation with ssRNA was shown to enhance follicular helper T (T FH ) function leading improved responses in vitro . We investigated whether this mechanism rescue an exhausted immune CHB infection. Effect of agonism on supporting cytokines and cells were evaluated using ex vivo assays. The ability oral agonist promote tested samples from phase 1b clinical trial. induced polarizing cytokine IL-12 monocytes. Treatment peripheral blood mononuclear (PBMCs) patients agonists IL-21 by enhanced + BCL-6 ICOS co-expression. Mechanistically, incubation isolated naïve CD4 triggered monocytes resulted their differentiation into dependent manner. Furthermore, co-culture these producing autologous led memory (CD19 CD27 plasma generation ++ CD38 IgG production. Importantly, treated agonist, HBsAg-specific BCL-6, ICOS, CD40L expression defective marker (AIM) along partial restoration ELISPOT evident. thus HBV-specific improving monocyte-mediated may play a role achieving HBV cure.