Renin-angiotensin system contributes to naive T-cell migration in vivo.
Angiotensin II (Ang II) plays an important role in the regulation of the T-cell response during inflammation. However, the cellular mechanisms underlying the regulation of lymphocytes under physiologic conditions have not yet been studied. Here, we tested the influence of Ang II on T-cell migration using T cells from BALB/c mice. The results obtained in vivo showed that when Ang II production or the AT1 receptor were blocked, T-cell counts were enhanced in blood but decreased in the spleen. The significance of these effects was confirmed by observing that these cells migrate, through fibronectin to Ang II via the AT1 receptor. We also observed a gradient of Ang II from peripheral blood to the spleen, which explains its chemotactic effect on this organ. The following cellular mechanisms were identified to mediate the Ang II effect: upregulation of the chemokine receptor CCR9; upregulation of the adhesion molecule CD62L; increased production of the chemokines CCL19 and CCL25 in the spleen. These results indicate that the higher levels of Ang II in the spleen and AT1 receptor activation contribute to migration of naive T cells to the spleen, which expands our understanding on how the Ang II/AT1 receptor axis contributes to adaptive immunity.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
J L
JL
Silva-Filho
Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
M C
MC
Souza
Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
M G
MG
Henriques
Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
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A
Morrot
Departamento de Imunologia, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
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W
Savino
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia e Bioimagem, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brazil.
C
C
Caruso-Neves
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brazil. Electronic address: acacia@biof.ufrj.br.
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AA
Pinheiro
D056704:Adaptive Immunity; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D054388:Receptors, CCR / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
C119309:CC chemokine receptor 9; C515461:Ccl19 protein, mouse; C491541:Ccl25 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; D044140:Receptor, Angiotensin, Type 1; D054388:Receptors, CCR; D054400:Receptors, CCR7; D016201:Receptors, Lymphocyte Homing; D000804:Angiotensin II; D019041:L-Selectin
Adaptive immunity; Angiotensin receptors; Chemokine; Lymphoid organs; Renin–angiotensin system