AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity

Abstract

Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including TH polarization. The multienzyme aminoacyl-tRNA synthetase complex component AIMp1/p43 responds to cellular stress and exerts pro-inflammatory functions; however, a role for DC-expressed AIMp1 in TH polarization has not previously been shown. Here, we demonstrate that the absence of AIMp1 in bone marrow-derived DC (BMDC) significantly impairs cytokine and costimulatory molecule expression, p38 MAPK signaling, and TH1 polarization of cocultured T-cells while significantly dysregulating immune-related gene expression. These deficits resulted in significantly compromised BMDC vaccine-mediated protection against melanoma. AIMp1 within the host was also critical for innate and adaptive antiviral immunity against influenza virus infection in vivo. Cancer patients with AIMp1 expression levels in the highest tertiles exhibited a 70% survival advantage at 15-year postdiagnosis as determined by bioinformatics analysis of nearly 9,000 primary human tumor samples in The Cancer Genome Atlas database. These data establish the importance of AIMp1 for the effective governance of antitumor and antiviral immune responses.

Aminoacyl-tRNA synthetases, therapeutic targets for infectious diseases

“…AIMP1 −/− BMDCs also expressed lower levels of costimulatory molecules and MHC class II following LPS treatment. The p38 MAPK signaling pathway was also significantly impaired in AIMP1 −/− BMDCs which reduced T H 1 polarization [21].…”

“…In agreement with our data, another group showed that AIMP1 is up-regulated after influenza A infection. This transcriptome analysis revealed that AIMP1 is closely related to antiviral immunity [21]. Microarray analysis of antigen-loaded wild-type (WT) or AIMP1 −/− mouse bone marrow-derived dendritic cells (BMDCs) showed that AIMP1 regulates a variety of immune processes through important antiviral genes including IFN-activated genes, IFN regulatory factor genes, and innate immune sensors such as 2′-5′-oligoadenylate synthase (Oas) family genes and Ddx58.…”

“…Recent studies identified novel molecular and cellular processes through which ARSs control host immune responses against infections [20][21][22]. EPRS contributes to innate antiviral immunity and promotes viral clearance [20].…”

“…EPRS contributes to innate antiviral immunity and promotes viral clearance [20]. The MSC protein AIMP1 also has a critical role in innate and adaptive antiviral immunity against influenza A virus infection [21]. In addition, secreted WRS acts as an early warning signal of host infections [22].…”

Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1‐Binding Proteins in Laryngeal Squamous Cell Carcinoma

“…AIMP1 is a multifunctional protein, originally identified as a non‐catalytic component of cytoplasmic arginyl‐tRNA synthase that stimulates its catalytic activity . Additional functions of AIMP1 have also been reported, such as promoting inflammation by activating monocytes macrophages and enhancing wound healing via fibroblast proliferation and collagen synthesis . Besides, AIMP1 also induces angiogenesis at low concentrations but inhibits angiogenesis at high concentrations .…”