Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Shaomin Hu, Kang Kang Yang, Jie Yang, Ming Li, Na Xiong

Producción científica: Articlerevisión exhaustiva

46 Citas (Scopus)

Resumen

Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper IgA production to maintain intestinal homeostasis and protect against infection. However, interfering with CCR10 or its ligand did not impair intestinal IgA production under homeostatic conditions or during infection, and the in vivo function of CCR10 in the intestinal IgA response remains unknown. We found that an enhanced generation of IgA + cells in isolated lymphoid follicles of intestines offset defective intestinal migration of IgA + cells in CCR10-KO mice, resulting in the apparently normal IgA production under homeostatic conditions and in primary response to pathogen infection. However, the compensatorily generated IgA + cells in CCR10-KOmice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA-producing plasma cells and IgA + memory B cells generated against the pathogen infection could not be maintained properly in intestines. Consequently, IgA memory responses to the pathogen reinfection were severely impaired in CCR10-KOmice. These findings elucidate critical roles of CCR10 in regulating the intestinal IgA response and memory maintenance and could help in design of vaccines against intestinal and possibly other mucosal pathogens.

Idioma originalEnglish (US)
Páginas (desde-hasta)E1035-E1044
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen108
N.º45
DOI
EstadoPublished - nov 8 2011
Publicado de forma externa

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