Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis

BACKGROUND: The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.

METHODS: IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin).

RESULTS: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP.

CONCLUSIONS: This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:79

Enthalten in:

Hypertension (Dallas, Tex. : 1979) - 79(2022), 10 vom: 25. Okt., Seite 2239-2249

Sprache:

Englisch

Beteiligte Personen:

Saha, Piu [VerfasserIn]
Mell, Blair [VerfasserIn]
Golonka, Rachel M [VerfasserIn]
Bovilla, Venugopal R [VerfasserIn]
Abokor, Ahmed A [VerfasserIn]
Mei, Xue [VerfasserIn]
Yeoh, Beng San [VerfasserIn]
Doris, Peter A [VerfasserIn]
Gewirtz, Andrew T [VerfasserIn]
Joe, Bina [VerfasserIn]
Vijay-Kumar, Matam [VerfasserIn]

Links:

Volltext

Themen:

B cells
Blood pressure
Flagellin
Gut microbiota
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Journal Article
Milk
Polymeric immunoglobulin receptors
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 09.09.2022

Date Revised 02.10.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1161/HYPERTENSIONAHA.122.19307

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM344698513