Τίτλος:
An integrin αEβ7-dependent mechanism of IgA transcytosis requires direct plasma cell contact with intestinal epithelium
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Efficient IgA transcytosis is critical for the maintenance of a homeostatic microbiota. In the canonical model, locally-secreted dimeric (d)IgA reaches the polymeric immunoglobulin receptor (pIgR) on intestinal epithelium via simple diffusion. A role for integrin αE(CD103)β7 during transcytosis has not been described, nor its expression by intestinal B cell lineage cells. We found that αE-deficient (αE−/−) mice have a luminal IgA deficit, despite normal antibody-secreting cells (ASC) recruitment, local IgA production and increased pIgR expression. This deficit was not due to dendritic cell (DC)-derived retinoic acid (RA) nor class-switching defects, as stool from RAG−/− mice reconstituted with αE−/− B cells was also IgA deficient. Flow cytometric, ultrastructural and transcriptional profiling showed that αEβ7-expressing ASC represent an undescribed subset of terminally-differentiated intestinal plasma cells (PC) that establishes direct cell to cell contact with intestinal epithelium. We propose that IgA not only reaches pIgR through diffusion, but that αEβ7+ PC dock with E-cadherin-expressing intestinal epithelium to directly relay IgA for transcytosis into the intestinal lumen. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Συγγραφείς:
Guzman, M.
Lundborg, L.R.
Yeasmin, S.
Tyler, C.J.
Zgajnar, N.R.
Taupin, V.
Dobaczewska, K.
Mikulski, Z.
Bamias, G.
Rivera-Nieves, J.
Περιοδικό:
Mucosal Immunology
Εκδότης:
Springer Nature BV
DOI:
10.1038/s41385-021-00439-x