Impaired T cell-Independent antibody responses and mucosal IgA production in Traf5-deficient mice
Abstract
Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an adaptor protein that mediates signaling downstream of multiple immunoregulatory receptors, including members of the tumor necrosis factor receptor superfamily. Although TRAF5 has been implicated in B-cell activation during T-cell-dependent humoral immune responses, its role in B-cell responses to a proliferation-inducing ligand (APRIL; TNFSF13) and T-cell-independent type 2 (TI-2) antibody responses remains poorly defined. Here, we show that Traf5 deficiency impairs antigen-specific IgG3 production during TI-2 immune responses and reduces fecal IgA levels. Traf5-deficient mice exhibited markedly reduced IgG3 responses to the TI-2 antigen 2,4,6-trinitrophenyl-conjugated Ficoll, whereas antigen-specific IgM production was preserved. In addition, Traf5 deficiency resulted in significantly decreased fecal IgA levels and reduced density of IgA+ cells in the colonic lamina propria, whereas the frequencies of IgA+ B cells in Peyer’s patches and the small intestine remained largely unchanged. T-cell and B-cell development was comparable between wild-type and Traf5-deficient mice. Although the expression of the APRIL receptor transmembrane activator and CAML interactor (TACI; TNFRSF13B) on splenic B cells was comparable between wild-type and Traf5-deficient mice, APRIL-induced expression of activation-induced cytidine deaminase (AID; encoded by Aicda) and IgA production in vitro were selectively impaired in Traf5-deficient splenic B cells, without affecting B-cell survival. Collectively, these findings indicate that TRAF5 contributes to optimal TI-2 immune responses and is associated with mucosal IgA production. The impaired APRIL-induced Aicda expression and IgA production observed in Traf5-deficient splenic B cells suggest that TRAF5 contributes to T-cell-independent humoral immunity.
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BibTeX
@article{hikosakakuniishi2026impaired,
title = {{Impaired T cell-Independent antibody responses and mucosal IgA production in Traf5-deficient mice}},
author = {Mari Hikosaka-Kuniishi and Ren Sunakawa and Soichiro Kobayashi and Fumiya Nakajima and Yuta Tsutsui and Kota Makara and Sayaka Ogawara and Chieri Iwata and Momoe Itsumi and Masashi Morita and Takanori So},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1875186},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1875186},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impaired T cell-Independent antibody responses and mucosal IgA production in Traf5-deficient mice
AU - Mari Hikosaka-Kuniishi
AU - Ren Sunakawa
AU - Soichiro Kobayashi
AU - Fumiya Nakajima
AU - Yuta Tsutsui
AU - Kota Makara
AU - Sayaka Ogawara
AU - Chieri Iwata
AU - Momoe Itsumi
AU - Masashi Morita
AU - Takanori So
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1875186
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1875186
AB - Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an adaptor protein that mediates signaling downstream of multiple immunoregulatory receptors, including members of the tumor necrosis factor receptor superfamily. Although TRAF5 has been implicated in B-cell activation during T-cell-dependent humoral immune responses, its role in B-cell responses to a proliferation-inducing ligand (APRIL; TNFSF13) and T-cell-independent type 2 (TI-2) antibody responses remains poorly defined. Here, we show that Traf5 deficiency impairs antigen-specific IgG3 production during TI-2 immune responses and reduces fecal IgA levels. Traf5-deficient mice exhibited markedly reduced IgG3 responses to the TI-2 antigen 2,4,6-trinitrophenyl-conjugated Ficoll, whereas antigen-specific IgM production was preserved. In addition, Traf5 deficiency resulted in significantly decreased fecal IgA levels and reduced density of IgA+ cells in the colonic lamina propria, whereas the frequencies of IgA+ B cells in Peyer’s patches and the small intestine remained largely unchanged. T-cell and B-cell development was comparable between wild-type and Traf5-deficient mice. Although the expression of the APRIL receptor transmembrane activator and CAML interactor (TACI; TNFRSF13B) on splenic B cells was comparable between wild-type and Traf5-deficient mice, APRIL-induced expression of activation-induced cytidine deaminase (AID; encoded by Aicda) and IgA production in vitro were selectively impaired in Traf5-deficient splenic B cells, without affecting B-cell survival. Collectively, these findings indicate that TRAF5 contributes to optimal TI-2 immune responses and is associated with mucosal IgA production. The impaired APRIL-induced Aicda expression and IgA production observed in Traf5-deficient splenic B cells suggest that TRAF5 contributes to T-cell-independent humoral immunity.
SN - 1664-3224
ER -