Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway

Chandra Nataraj, Michael I. Oliverio, Roslyn B. Mannon, Peter J. Mannon, Laurent P. Audoly, Carmen S. Amuchastegui, Phillip Ruiz, Oliver Smithies, Thomas M. Coffman

Research output: Contribution to journalArticle

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Abstract

The renin-angiotensin system (RAS) is a key regulator of vascular tone and blood pressure. In addition, angiotensin II also has a number of cellular effects that may contribute to disease pathogenesis. Using Agtr1a(-/-) mice, which lack AT(1A) receptors for angiotensin II, we have identified a novel function of the RAS to modulate the immune system. We find that angiotensin II, acting through type 1 (AT1) receptors on immune cells, triggers the proliferation of splenic lymphocytes. These actions contribute to the vigor of cellular alloimmune responses. Within lymphoid organs, sufficient components of the RAS are present to activate AT1 receptors during an immune response, promoting cell growth. These actions require activation of calcineurin phosphatase. In an in vivo model of cardiac transplantation, the absence of AT1 signaling accentuates the immunosuppressive effects of the calcineurin inhibitor cyclosporine. We conclude that inhibition of AT1 receptor signaling should be useful as an anti-inflammatory and immunosuppressive therapy. Furthermore, the actions of the RAS to promote lymphocyte activation may contribute to inflammation that characterizes a number of diseases of the heart and the vascular system.

Original languageEnglish
Pages (from-to)1693-1701
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number12
StatePublished - Dec 1 1999

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Calcineurin
Renin-Angiotensin System
Cellular Immunity
Angiotensin II
Immunosuppressive Agents
Angiotensin Receptors
Heart Transplantation
Lymphocyte Activation
Vascular Diseases
Cyclosporine
Blood Vessels
Immune System
Heart Diseases
Anti-Inflammatory Agents
Cell Proliferation
Lymphocytes
Blood Pressure
Inflammation
Growth
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nataraj, C., Oliverio, M. I., Mannon, R. B., Mannon, P. J., Audoly, L. P., Amuchastegui, C. S., ... Coffman, T. M. (1999). Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. Journal of Clinical Investigation, 104(12), 1693-1701.

Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. / Nataraj, Chandra; Oliverio, Michael I.; Mannon, Roslyn B.; Mannon, Peter J.; Audoly, Laurent P.; Amuchastegui, Carmen S.; Ruiz, Phillip; Smithies, Oliver; Coffman, Thomas M.

In: Journal of Clinical Investigation, Vol. 104, No. 12, 01.12.1999, p. 1693-1701.

Research output: Contribution to journalArticle

Nataraj, C, Oliverio, MI, Mannon, RB, Mannon, PJ, Audoly, LP, Amuchastegui, CS, Ruiz, P, Smithies, O & Coffman, TM 1999, 'Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway', Journal of Clinical Investigation, vol. 104, no. 12, pp. 1693-1701.
Nataraj C, Oliverio MI, Mannon RB, Mannon PJ, Audoly LP, Amuchastegui CS et al. Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. Journal of Clinical Investigation. 1999 Dec 1;104(12):1693-1701.
Nataraj, Chandra ; Oliverio, Michael I. ; Mannon, Roslyn B. ; Mannon, Peter J. ; Audoly, Laurent P. ; Amuchastegui, Carmen S. ; Ruiz, Phillip ; Smithies, Oliver ; Coffman, Thomas M. / Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 12. pp. 1693-1701.
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