CC chemokine ligands 25 and 28 play essential roles in intestinal extravasation of IgA antibody-secreting cells.
CCL25 (also known as thymus-expressed chemokine) and CCL28 (also known as mucosae-associated epithelial chemokine) play important roles in mucosal immunity by recruiting IgA Ab-secreting cells (ASCs) into mucosal lamina propria. However, their exact roles in vivo still remain to be defined. In this study, we first demonstrated in mice that IgA ASCs in small intestine expressed CCR9, CCR10, and CXCR4 on the cell surface and migrated to their respective ligands CCL25, CCL28, and CXCL12 (also known as stromal cell-derived factor 1), whereas IgA ASCs in colon mainly expressed CCR10 and CXCR4 and migrated to CCL28 and CXCL12. Reciprocally, the epithelial cells of small intestine were immunologically positive for CCL25 and CCL28, whereas those of colon were positive for CCL28 and CXCL12. Furthermore, the venular endothelial cells in small intestine were positive for CCL25 and CCL28, whereas those in colon were positive for CCL28, suggesting their direct roles in extravasation of IgA ASCs. Consistently, in mice orally immunized with cholera toxin (CT), anti-CCL25 suppressed homing of CT-specific IgA ASCs into small intestine, whereas anti-CCL28 suppressed homing of CT-specific IgA ASCs into both small intestine and colon. Reciprocally, CT-specific ASCs and IgA titers in the blood were increased in mice treated with anti-CCL25 or anti-CCL28. Anti-CXCL12 had no such effects. Finally, both CCL25 and CCL28 were capable of enhancing alpha4 integrin-dependent adhesion of IgA ASCs to mucosal addressin cell adhesion molecule-1 and VCAM-1. Collectively, CCL25 and CCL28 play essential roles in intestinal homing of IgA ASCs primarily by mediating their extravasation into intestinal lamina propria.
Hieshima
Kunio
K
Department of Microbiology, Kinki University School of Medicine, Osaka, Japan.
Kawasaki
Yuri
Y
Hanamoto
Hitoshi
H
Nakayama
Takashi
T
Nagakubo
Daisuke
D
Kanamaru
Akihisa
A
Yoshie
Osamu
O
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D054425:Chemokine CCL27; D054377:Chemokine CXCL12; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D019742:Chemokines, CC / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007136:Immunoglobulins / Q000378:metabolism; D007150:Immunohistochemistry; D039441:Integrin alpha4 / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009088:Mucoproteins / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D054388:Receptors, CCR; D054447:Receptors, CCR10; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013194:Staining and Labeling; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; C492276:CCL27 protein, human; C414047:CCL28 protein, human; C515706:CCR10 protein, human; C515255:CXCL12 protein, human; C491541:Ccl25 protein, mouse; C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; D015815:Cell Adhesion Molecules; D054425:Chemokine CCL27; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D007106:Immune Sera; D007070:Immunoglobulin A; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D054388:Receptors, CCR; D054447:Receptors, CCR10; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D002772:Cholera Toxin