Interferon lambda 4 can directly activate human CD19⁺ B cells and CD8⁺ T cells

Abstract

Compared with the ubiquitous expression of type I (IFNα and IFNβ) interferon receptors, type III (IFNλ) interferon receptors are mainly expressed in epithelial cells of mucosal barriers of the of the intestine and respiratory tract. Consequently, IFNλs are important for innate pathogen defense in the lung and intestine. IFNλs also determine the outcome of hepatitis C virus (HCV) infections, with IFNλ4 inhibiting spontaneous clearance of HCV. Because viral clearance is dependent on T cells, we explored if IFNλs can directly bind to and regulate human T cells. We found that human B cells and CD8+ T cells express the IFNλ receptor and respond to IFNλs, including IFNλ4. IFNλs were not inhibitors but weak stimulators of B- and T-cell responses. Furthermore, IFNλ4 showed neither synergistic nor antagonistic effects in co-stimulatory experiments with IFNλ1 or IFNα. Multidimensional flow cytometry of cells from liver biopsies of hepatitis patients from IFNλ4-producers showed accumulation of activated CD8+ T cells with a central memory-like phenotype. In contrast, CD8+ T cells with a senescent/exhausted phenotype were more abundant in IFNλ4–non-producers. It remains to be elucidated how IFNλ4 promotes CD8 T-cell responses and inhibits the host immunity to HCV infections.

Regulation and Function of Interferon-Lambda (IFNλ) and Its Receptor in Asthma

“…This effect is due to an altered migratory and antigen presentation ability of CD103+ DC ( 57 ). Both, IFNλ1 and IFNλ4, even have synergistic effects with low dose TCR-mediated stimulation and were able to enhance IFNγ production by CD8+ T cells ( 58 ). Further, peripheral DC stimulated with IFNλ upregulated CD80 and ICOS-L expression and, in combination with IFNα, an even stronger enhancement of CD80, CD83 and ICOS-L was observed ( 59 ).…”

Interferon Lambda: An Anonymous Warrior of Host-Microbial Fray in The Pathogenesis of Periodontal Diseases

“…12,13 Furthermore, IFN-λs has an impact on immune cells in response to viral infection by limiting viral replication, lowering viral load, and delaying the development of viral drug resistance, resulting in the development of antiviral immunity. [14][15][16][17][18][19][20][21] Due to the scarcity of researches, the precise involvement of IFN-λs in non-viral inflammatory conditions is yet be precisely investigated. IFN-λs are primarily expressed by epithelial cells, but myeloid cells, neutrophils, B lymphocytes, and dendritic cells have also been found to express IFN-λs.…”

Interferon-lambda: New functions on intestinal symptoms in COVID-19

“…To date, IFN-λ1-4 is considered to regulate the immune response, including the upregulation of IL-6, IL-8, and the downregulation of IL-10 in peripheral blood mononuclear cells (PBMCs)[ 79 ]. It also alters Th1/Th2 T-cell balance, reduces IL-13 production by T cells[ 80 ], and induces ISGs in B cells and plasmacytoid dendritic cells, as well as in CD8 T cells, especially effector memory cells (TEMRA)[ 81 ] (Figure 2 ). As an anti-inflammatory factor, IL-10 induction in macrophages provides a powerful pathogen immune escape mechanism, which causes chronic infection[ 82 ].…”