Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression.
Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TβRIII) and activation of canonical TGF-β signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α (GLα) transcription and GLα promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and α4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9+IgA+plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Jeong-Min
JM
Lee
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Young-Saeng
YS
Jang
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Bo-Ra
BR
Jin
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Sun-Jin
SJ
Kim
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Hyeon-Jin
HJ
Kim
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
Bo-Eun
BE
Kwon
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
Hyun-Jeong
HJ
Ko
Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Sung-Il
SI
Yoon
College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
Geun-Shik
GS
Lee
Department of Animal Life and Environmental Science, College of Agriculture and Life Science, Hankyong National University, Anseong-si 456-749, Republic of Korea.
Woan-Sub
WS
Kim
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Goo-Young
GY
Seo
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
Pyeung-Hyeun
PH
Kim
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007781:Lactoferrin / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D007070:Immunoglobulin A; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D014212:Tretinoin; D007781:Lactoferrin