NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection

Abstract

NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis.

miR‐190b promotes tumor growth and metastasis via suppressing NLRC3 in bladder carcinoma

“…NLRC3 has been shown to participate in a lot of pathological processes. For example, Hu et al reported that NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection . Guo et al demonstrated that NLRC3 promotes host resistance against Pseudomonas aeruginosa ‐induced keratitis by promoting the degradation of interleukin 1 receptor associated kinase 1 (IRAK1) .…”

NLRC 3 expression in dendritic cells attenuates CD 4 + T cell response and autoimmunity

“…Although NLRC3 has been demonstrated as a negative regulator in macrophages and T cells (Schneider et al, 2012;Zhang et al, 2014;Hu et al, 2018), the specific role of NRLC3 in DCs still remains poorly understood. In the presence of DC-maturing stimuli, DCs uptake antigens and mature to become the most potent antigenpresenting cells accompanied by upregulation of MHC II and costimulatory molecules (Guermonprez et al, 2002).…”

“…It has been reported that NLRC3 is expressed by many types of cells, including T cells (Hu et al, 2018;Uchimura et al, 2018) that influence activity of DCs via their interactions. Thus, it still remains unclear about the direct contribution of NLRC3 regulates DCs during EAE progression.…”

“…NLRC3 deficiency in T cells or macrophages results in increased NF-jB p65 phosphorylation (Schneider et al, 2012;Hu et al, 2018). NLRC3 deficiency in T cells or macrophages results in increased NF-jB p65 phosphorylation (Schneider et al, 2012;Hu et al, 2018).…”

“…NLRC3 deficiency in T cells or macrophages results in increased NF-jB p65 phosphorylation (Schneider et al, 2012;Hu et al, 2018). It has also been shown that NLRC3 suppresses the activation of CD4 + T via negatively modulating the ERK signaling pathway in CD4 + T cells (Hu et al, 2018). It has also been shown that NLRC3 suppresses the activation of CD4 + T via negatively modulating the ERK signaling pathway in CD4 + T cells (Hu et al, 2018).…”