Mechanism of up‐regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide

Abstract

Summary The mechanisms by which immunoglobulin A (IgA) production up‐regulates in the intestine of Toll‐like receptor‐4 (TLR4)‐mutated mice were investigated. When TLR4‐mutated, C3H/HeJ and BALB/lpsd mice received oral administration of cholera toxin (CT), not only CT‐specific IgA levels in the intestinal lavage but also the number of IgA‐producing cells in intestinal lamina propria (iLP) significantly increased compared with those of the wild‐type C3H/He and BALB/c mice. Interleukin (IL)‐5‐producing cells and CD86+ cells in iLP also significantly increased in C3H/HeJ mice. The expression of major histocompatibility complex class II and CD86 on cells present in Peyer's patches (PPs) of C3H/HeJ mice was higher than those of C3H/He mice. In non‐immunized C3H/HeJ mice, the expression of transforming growth factor‐β (TGF‐β) mRNA and the percentages of IL‐10‐producing cells in PPs but not in spleen increased when compared with those in C3H/He mice. The suppressor of cytokine signalling‐1 (SOCS‐1) was expressed in PPs of C3H/He mice but not C3H/HeJ mice. These results indicate that high IgA levels in the intestine of TLR4‐mutated mice are due to up‐regulation of TGF‐β and IL‐10 and the lack of regulation by SOCS‐1.

Role of Toll-like receptors in host responses to a virulence antigen of Streptococcus mutans expressed by a recombinant, attenuated Salmonella vector vaccine

“…In the present study, we observed significantly lower salivary IgA anti-SBR and anti- Salmonella responses in MyD88 −/− compared to wt mice following the initial and booster immunizations. This finding was not totally unexpected, since previous studies have suggested that MyD88 is essential for class switching of naïve B cells to IgA committed B cells and for differentiation of IgA committed B cells to IgA- producing cells [40]. However, others have reported that MyD88 was not essential for the induction of a mucosal IgA response to a recombinant attenuated Salmonella vaccine [30, 31].…”

Mucosal-associated invariant T cells and disease

“…The suppression of EAE by invariant Vα19TCR + T cells is associated with reduced expression of pro-inflammatory molecules and increased production of IL-10 by B cells, through an inducible T cell co-stimulator-dependent interaction with invariant Vα19TCR + T cells 126 . IL-10 can inhibit excessive gut inflammation 127 and is implicated in IgA production 128 . A regulatory role of IL-10-secreting MAIT cells is also suggested by their presence in the adipose tissue of lean individuals but their reduced frequency in obese individuals 73 .…”

Increases in IgA+ B cells in Peyer's patches during milk-borne mouse mammary tumor virus infection are influenced by Toll-like receptor 4 and are completely dependent on the superantigen response

“…It has been reported that TLR4-deficient C3H/HeJ mice have elevated IgA responses (Kaneko et al, 2005;Kiyono et al, 1980). Interestingly, in this paper we show that the increase in IgA + B cells is significantly lower in TLR4-deficient mice than in the wild-type controls (P,0.05).…”

“…TLRs function as sensors of infection and are critical for the initiation of innate and adaptive immune responses. It has been reported that TLR4-deficient C3H/HeJ mice have more potent IgA responses than TLR4-sufficient C3H/HeN mice (Kaneko et al, 2005;Kiyono et al, 1980). Interestingly, it has been shown that MMTV is able to interact with B cells and DCs through TLR4.…”