Figure - available from: Clinical & Translational Immunology
This content is subject to copyright. Terms and conditions apply.
NK cell involvement in autoimmune inflammatory diseases. NK cells exacerbate RA by secreting soluble mediators such as (a) M‐CSF and RANKL that drive the differentiation of bone‐eroding osteoclasts and (b) GM‐CSF that promotes the production of pro‐inflammatory mediators by joint‐infiltrating neutrophils. (c) NK cells do not appear to play a dominant role in MS but boosting their cytotoxic function with anti‐NKG2A may eliminate encephalitogenic Th17 cells and alleviate disease in the EAE model. (d) NK cells may promote SLE through their interaction with pDCs via LFA‐1 and DNAM‐1 that enhances the production of cytokines and chemokines such as IFN‐α, IFN‐γ, TNF‐α, IL‐6, IL‐8, CCL3 and CCL4. NK cells are also found in kidney of lupus nephritis patients but it remains unclear if NK cells and their cytokine dysfunction contribute to tissue pathology. (e) NK cells could contribute to the generation of autoantigens through excessive killing of CV‐B4‐infected pancreatic β islets. However, other functions of NK cells such as IFN‐γ production remain unclear and future studies are required to capture phenotypic and functional diversity of NK cells in both CV‐B4‐associated and sterile T1DM subtypes. (f) Alveolar NK cells are thought to give rise to autoantigens such as histidyl tRNA synthetase following respiratory insults in anti‐synthetase syndrome. Future studies are needed to evaluate whether similar numerical and functional changes in NK cells occur in the discrete subtype of IIM.
Source publication
Natural killer (NK) cells are a specialised population of innate lymphoid cells (ILCs) that help control local immune responses. Through natural cytotoxicity, production of cytokines and chemokines, and migratory capacity, NK cells play a vital immunoregulatory role in the initiation and chronicity of inflammatory and autoimmune responses. Our unde...
Similar publications
The manifestations of COVID-19 have been evolving over time. Various post-COVID-19 syndromes are being recognised. Various viruses have been implicated in the pathogenesis of autoimmune diseases, and we expect a similar outcome with the severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 virus penetrates various...
Citations
... Another consideration in the search of immune targets is, that many immune cells do not exclusively possess pro-or antiinflammatory properties as they often have effector functions in both directions. This duality is exemplified in experiments with knock-out mice, where the complete elimination of CD8 + or NK cells -both assumed to be involved in MS immunopathogenesisresulted in disease exacerbation (53,54). ...
Background
The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
Methods
We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
Results
We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
Conclusion
In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
... This NK population was already described in SLE 31,52 , children with high risk for type I diabetes 53 and in multiple sclerosis patients with clinical relapse 36 . Although no functional studies have been performed in humans, the evidence from mouse models suggests that these cells possess both NK-like and DC-like functions, being able to produce type I and II IFNs, perform antigen presentation, and trigger a lupus-like disease 51 . Our data highlight the need for further characterization of these NK cells in the context of the other SADs. ...
Background: Systemic autoimmune diseases (SADs) are characterized by internal heterogeneity, overlapping clinical symptoms, and shared molecular pathways. Therefore, they are difficult to diagnose and new tools allowing precise diagnosis are needed. Molecular-based reclassification studies enable to find patterns in a diagnosis-independent way.
Objective: To evaluate the possibility of using high-content immunophenotyping for detecting patient subgroups in the context of precise treatment.
Methods: Whole blood high-content immunophenotyping of 101 patients with 7 systemic autoimmune diseases and 22 controls was performed using 36-plex mass cytometry panel. Patients were compared across diagnostic entities and re-classified using Monte Carlo reference-based consensus clustering. Levels of 45-plex multiplexed cytokine were measured and used for cluster characterization.
Results: Differential analysis by diagnosis did not reveal any disease-specific pattern in the cellular compositions and phenotypes but rather their relative similarities. Accordingly, patients were classified into phenotypically distinct groups composed of different diagnostic entities sharing common immunophenotypes and cytokine signatures. These features were mainly based on granulocyte activation and CD38 expression in discrete lymphocyte populations and were related to Th17 or IFN-dependent cytokines.
Conclusions: Our data indicate that specific individuals could potentially benefit from the same line of treatment independently of their diagnosis and emphasize the possibility of using immunophenotyping as a stratification tool in precision rheumatology.
... There is evidence that jSLE has stronger genetic background and interferon (IFN) signature (1)(2)(3). Although self-reactive T and B lymphocytes are critically linked to lupus development, others cells as neutrophils, monocytes, and natural killer (NK) cells have also been implicated (1,(4)(5)(6). Lupus pathogenesis is mainly ascribed to increased production and/or inefficient removal of dead cell debris (1,4,(7)(8)(9)(10)(11)(12). In this regard, our group demonstrated that patients with jSLE have altered expressions of the apoptosis-related proteins Fas and Bcl-2 in lymphocytes and monocytes, as well as altered sFas, sTRAIL, sFasL, and sMer levels, which related to disease activity and/or nephritis (13)(14)(15)(16)(17). ...
... NK are innate, CD3-negative, cells that comprise 5% to 15% of peripheral blood mononuclear components and lack antigen specificity (5). NK cells detect and have critical cytolytic effector role in response to intracellular pathogens and transformed or stressed cells (5). ...
... NK are innate, CD3-negative, cells that comprise 5% to 15% of peripheral blood mononuclear components and lack antigen specificity (5). NK cells detect and have critical cytolytic effector role in response to intracellular pathogens and transformed or stressed cells (5). NK cell cytotoxicity is regulated by a series of cytokines including IFN-a and IFN-g (5,18). ...
Background
Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement.
Methods
Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3−CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels.
Results
Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = −0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls.
Conclusion
This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell–based.
... Contributed to NK Cell Activation in the PBMC Culture. Secretion of perforin, IFN-γ, and granzymes are classified as the markers for NK cell activation during infection, tumor development, and autoimmunity progression [7,[57][58][59][60]. Thus, we studied whether γc cytokines can modulate the production of these soluble factors to evaluate the NK cell activation status. ...
Natural killer (NK) cell is an essential cytotoxic lymphocyte in our innate immunity. Activation of NK cells is of paramount importance in defending against pathogens, suppressing autoantibody production and regulating other immune cells. Common gamma chain (γc) cytokines, including IL-2, IL-15, and IL-21, are defined as essential regulators for NK cell homeostasis and development. However, it is inconclusive whether γc cytokine-driven NK cell activation plays a protective or pathogenic role in the development of autoimmunity. In this study, we investigate and correlate the differential effects of γc cytokines in NK cell expansion and activation. IL-2 and IL-15 are mainly responsible for NK cell activation, while IL-21 preferentially stimulates NK cell proliferation. Blockade of Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by either JAK inhibitors or antibodies targeting γc receptor subunits reverses the γc cytokine-induced NK cell activation, leading to suppression of its autoimmunity-like phenotype in vitro. These results underline the mechanisms of how γc cytokines trigger autoimmune phenotype in NK cells as a potential target to autoimmune diseases.
... Monocytes, macrophages, and dendritic cells, among other innate immune cells, are participating in the inflammatory reactions in RA cases along with activating the acquired immune response, which is crucial in the late stages of the disease. [3,10] The novelty of this work is the first in our society to correlate IL-12 with vitamin D3 (VD3), anti-CCP, and RF levels as markers for rheumatoid disease. ...
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Abstract Background: Rheumatoid arthritis (RA) is an autoimmune disorder involving the synovial joints of humans. Recent research has demonstrated that vitamin D (VD3) can influence a person's susceptibility to RA, and a proinflammatory mediator affects the pathogenesis of RA. Objectives: This work aimed to investigate the correlation of VD3 with autoantibodies and interleukin-12 (IL-12) in RA patients. Materials and Methods: Eighty women were included in this case-control study: 60 confirmed RA and 20 healthy controls (HC) in the age range of 29-71 years. The sera of study subjects were examined for anti-cyclic citrullinated peptides (anti-CCP), vitamin D3, and IL-12 by enzyme-linked immunosorbent assay. Rheumatoid factor (RF-IgG) was tested by latex agglutination technique. Results: The present findings revealed a significantly high concentration of anti-CCP, RF-IgG, and IL-12 in RA patients in comparison to HC. The anti-CCP expressed high sensitivity and specificity at 80% and 100% compared to RF-IgG at 76.6% and 90%, respectively. Both RA patients and HC groups showed lower levels of VD3 with a nonsignificant difference; 50% of RA patients and 55% of the HC had vitamin D deficiency (<20 ng/mL). In RA patients, negative associations were observed between VD3 and anti-CCP and IL-12 levels. In contrast, a positive correlation was observed between anti-CCP and IL-12 in RA women. Conclusion: Anti-CCP had a better diagnostic value than RF. Low vitamin D is prevalent in RA patients and HC. Also, IL-12 may possess a vital role in RA's pathophysiology and inflammatory activity, along with IL-12 inhibition may be beneficial in treating this disease.
... These cells are mostly CD16 positive, showing high cell-killing ability. 13 In contrast, the minority population of circulating CD56 bright NK cells (10%) is generally considered cytokine-producing regulatory cells. 13 Moreover, NK cells are known to produce a variety of cytokines depending on the inflammatory microenvironment, such as IFN-γ, IL-4 and IL-10, and exert profound effects on the immune response. ...
... 13 In contrast, the minority population of circulating CD56 bright NK cells (10%) is generally considered cytokine-producing regulatory cells. 13 Moreover, NK cells are known to produce a variety of cytokines depending on the inflammatory microenvironment, such as IFN-γ, IL-4 and IL-10, and exert profound effects on the immune response. 3,14,15 Our previous results revealed a specific subpopulation of NK cells expressing CXCR5 and highlighted the different roles of CXCR5 + NK cells and CXCR5 -NK cells in EAMG. ...
... NK cell percentage and IFN-γ production were decreased in the peripheral blood of patients with aggravated MG Many studies have reported that several autoimmune diseases are associated with impaired NK cell proportion or function. 3,13 However, the changes in NK cells in MG remain controversial. Since multiple subsets of NK cells have been clearly identified and the complexity of NK cells is increasingly recognised, we analysed diverse NK cell subsets in the blood of controls and patients with MG. ...
Objectives:
Myasthenia gravis (MG) is a classic autoantibody-mediated disease in which pathogenic antibodies target postsynaptic membrane components, causing fluctuating skeletal muscle weakness and fatigue. Natural killer (NK) cells are heterogeneous lymphocytes that have gained increasing attention owing to their potential roles in autoimmune disorders. This study will investigate the relationship between the distinct NK cell subsets and MG pathogenesis.
Methods:
A total of 33 MG patients and 19 healthy controls were enrolled in the present study. Circulating NK cells, their subtypes and follicular helper T cells were analysed by flow cytometry. Serum acetylcholine receptor (AChR) antibody levels were determined by ELISA. The role of NK cells in the regulation of B cells was verified using a co-culture assay.
Results:
Myasthenia gravis patients with acute exacerbations had a reduced number of total NK cells, CD56dim NK cells and IFN-γ-secreting NK cells in the peripheral blood, while CXCR5+ NK cells were significantly elevated. CXCR5+ NK cells expressed a higher level of ICOS and PD-1 and a lower level of IFN-γ than those in CXCR5- NK cells and were positively correlated with Tfh cell and AChR antibody levels. In vitro experiments demonstrated that NK cells suppressed plasmablast differentiation while promoting CD80 and PD-L1 expression on B cells in an IFN-γ-dependent manner. Furthermore, CXCR5- NK cells inhibited plasmablast differentiation, while CXCR5+ NK cells could more efficiently promote B cell proliferation.
Conclusion:
These results reveal that CXCR5+ NK cells exhibit distinct phenotypes and functions compared with CXCR5- NK cells and might participate in the pathogenesis of MG.
... Using anti-asialoGM1, the NK cell depletion in the model reduced both bone erosion and joint inflammation [14]. According to recent research, chemokine receptors (i.e., CCR1, CCR5, and CXCR3) are expressed by synovial NK cells, which can facilitate the recruitment of inflammatory cells (driven by their respective chemokines) into the RA synovium [16], prime effector myeloid cells, and aggravate arthritis by producing inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage (M)-CSF, and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) [17,18]. ...
Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressive effects were observed in human peripheral blood mononuclear cell cultures and purified NK cells from healthy donors, as well as in purified NK cells from patients with rheumatoid arthritis. TP treatment induced downregulation of NK-activating receptor (CD54, CD69) expression and IFN-gamma secretion, in a dose-dependent manner. When exposed to K562 target cells, TP treatment induced inhibition of surface expression of CD107a and IFN-gamma synthesis in NK cells. Furthermore, TP treatment induced activation of inhibitory signaling (SHIP, JNK) and inhibition of MAPK signaling (p38). Thus, our findings demonstrate a previously unknown role for TP in NK cell functional suppression and reveal several key intracellular signaling that can be regulated by TP. Our findings also offer new insight into mechanisms of TP therapeutic treatment in autoimmune disease.
... The levels of peripheral Treg cells in DM patients are also lower than that in normal persons, possibly due to the regulation of RUNX3-Foxp3 by HAGLR (52,53). Nature killer (NK) cells, a subset of innate lymphoid cells, play an important role in inflammation and autoimmune responses via cell migration, cytotoxicity, and cytokine production (54). However, the specific mechanism of NK cells remains unclear in IIMs (54). ...
... Nature killer (NK) cells, a subset of innate lymphoid cells, play an important role in inflammation and autoimmune responses via cell migration, cytotoxicity, and cytokine production (54). However, the specific mechanism of NK cells remains unclear in IIMs (54). According to our CIBERSORT results, there were only resting NK cells in normal muscle tissue. ...
... But in DM muscle, the resting NK cells significantly decreased and the activated NK cells significantly increased. In previous studies, the levels of periphery NK cells in DM patients were decreased, which may be related to NK cells migration into muscle (54,55). Therefore, we speculated that the upregulation of activating NK cells infiltration in DM muscle was related to the migration of peripheral cells and the activation of resting NK cells in muscle. ...
Background
Dermatomyositis (DM) is a rare autoimmune disease characterized by severe muscle dysfunction, and the immune response of the muscles plays an important role in the development of DM. Currently, the diagnosis of DM relies on symptoms, physical examination, and biopsy techniques. Therefore, we used machine learning algorithm to screen key genes, and constructed and verified a diagnostic model composed of 5 key genes. In terms of immunity, The relationship between 5 genes and immune cell infiltration in muscle samples was analyzed. These diagnostic and immune-cell-related genes may contribute to the diagnosis and treatment of DM.
Methods
GSE5370 and GSE128470 datasets were utilised from the Gene Expression Omnibus database as DM test sets. And we also used R software to merge two datasets and to analyze the results of differentially expressed genes (DEGs) and functional correlation analysis. Then, we could detect diagnostic genes adopting least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) analyses. The validity of putative biomarkers was assessed using the GSE1551 dataset, and we confirmed the area under the receiver operating characteristic curve (AUC) values. Finally, CIBERSORT was used to evaluate immune cell infiltration in DM muscles and the correlations between disease-related biomarkers and immune cells.
Results
In this study, a total of 414 DEGs were screened. ISG15, TNFRSF1A, GUSBP11, SERPINB1 and PTMA were identified as potential DM diagnostic biomarkers(AUC > 0.85),and the expressions of 5 genes in DM group were higher than that in healthy group (p < 0.05). Immune cell infiltration analyses indicated that identified DM diagnostic biomarkers may be associated with M1 macrophages, activated NK cells, Tfh cells, resting NK cells and Treg cells.
Conclusion
The study identified that ISG15, TNFRSF1A, GUSBP11, SERPINB1 and PTMA as potential diagnostic biomarkers of DM and these genes were closely correlated with immune cell infiltration.This will contribute to future studies in diagnosis and treatment of DM.
... Disproportionate ILC are implicated in numerous autoimmune diseases, such as type I diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, psoriasis and spondylarthritis. 11,12 In MS, increased circulatory pro-inflammatory helper ILC1 and ILC3 have been described in untreated MS patients, 13,14 as well as increased ILC3 in CSF during early stages of MS. 15 By contrast, NK cells, in particular the CD56 bright subpopulation, have been suggested as immunoregulatory, with observed increases under various disease-modifying treatments (DMTs). 16 Here, we present the results of a comprehensive analysis of the entire ILC compartment in peripheral blood mononuclear cells (PBMC) in MS patients treated or untreated with alemtuzumab. ...
Objectives:
The role of innate lymphoid cells (ILC), particularly helper ILC, in the pathogenesis of multiple sclerosis (MS) is not well understood. Here, we present a comprehensive analysis of peripheral ILC subsets in MS patients prior and after alemtuzumab administration using mass cytometry.
Methods:
Circulating ILC were analysed by mass cytometry in MS patients before and after alemtuzumab. These were compared with non-MS controls. MS-related shifts among ILC immunophenotypes were further elucidated by fast interpolation-based t-SNE (Flt-SNE) dimensionality reduction.
Results:
Neither natural killer (NK) cells nor helper ILC (ILC1, ILC2 and ILC3) levels were altered following alemtuzumab treatment. However, CD56bright NK cell expansions were observed in relapsing patients. MS patients prior to alemtuzumab further displayed proportional shifts from ILC1 to ILC2, with MS-associated decreases in CCR6+ helper ILC proportions.
Conclusion:
CD56bright NK cells during relapse indicate an immediate response to disease reactivation, while CCR6-related shifts among helper ILC suggest altered ILC migration to the CNS during MS.
... 19 However, unlike B and T cells, NK cells do not undergo negative selection to acquire self-tolerance. 18 NK cells have been implicated in disorders that specifically involve BAFF and BAFFmediated signaling, [20][21][22] but the direct impact of this signaling pathway on NK cell function remains unclear. ...
... Functional NK cell defects have been reported in patients diagnosed with SLE. 21 Moreover, hematopoietic stem cells from patients with SLE displayed less capacity to differentiate into mature NK cells than those from healthy controls. 27 While the mechanisms underlying the reduced NK cell numbers and their functional deficiencies are not well understood, several NK cellassociated defects in patients with SLE have been characterized. ...
... These include reduced IL2Rβ expression, hyporesponsiveness to IL-15-mediated stimulation and suppression by antilymphocyte antibodies. 21 Reduced NK cell numbers and activity have also been reported in patients diagnosed with primary Sjögren's syndrome. 28 Treatment of a cohort of patients with Sjögren's syndrome using belimumab resulted in increased numbers of NK cells in both the blood and salivary glands. ...
The role of BAFF in B lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defence against viruses and tumours, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild‐type (WT), BAFF‐/‐, BAFF‐R‐/‐, TACI‐/‐, BCMA‐/‐, and BAFF transgenic (Tg) mice, we observed that BAFF signalling through BAFF‐R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF‐/‐ and BAFF Tg mice produced interferon‐γ and killed tumour cells at a similar level to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.
