Retnla (relmalpha/fizz1) suppresses helminth-induced Th2-type immunity

Area of Science:

• Immunology
• Parasitology

Background:

• Resistin-like molecule alpha (Retnla) is induced by Th2 cytokines, but its function in Th2 immunity is unclear.
• Th2-type immune responses are crucial for defense against helminth parasites.

Purpose of the Study:

• To investigate the role of Retnla in Th2-type immunity and helminth infection using Retnla-deficient mice.
• To determine if Retnla acts as a positive or negative regulator of Th2 responses.

Main Methods:

• Utilized Retnla(-/-) knockout mice and three distinct helminth infection models (Schistosoma mansoni, Nippostrongylus brasiliensis).
• Assessed pulmonary granuloma formation, eosinophil counts, serum IgE levels, liver fibrosis, and parasite expulsion.
• Analyzed immune responses through cytokine profiling and exogenous rRelmalpha treatment.

Main Results:

• Retnla deficiency exacerbated pulmonary granuloma formation, eosinophilia, and IgE production in response to S. mansoni.
• Absence of Retnla augmented liver inflammation, fibrosis, and hepatosplenic disease progression.
• Retnla(-/-) mice showed intensified lung pathology, reduced fecundity, and accelerated parasite expulsion with N. brasiliensis infection, indicating enhanced Th2 immunity.
• Retnla expression was dependent on IL-4/IL-13 and inhibited by IFN-gamma, with primary production by eosinophils and epithelial cells.

Conclusions:

• Retnla acts as a negative regulator of Th2-dependent immune responses.
• Retnla suppresses host resistance to helminth infections, including pulmonary granulomatous inflammation and fibrosis.
• Targeting Retnla may offer therapeutic potential for modulating Th2-mediated pathologies.