Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine

Valeri, Viviana; Tonon, Silvia; Vibhushan, Shamila; Gulino, Alessandro; Belmonte, Beatrice; Ádori, Mónika; Hedestam, Gunilla B. Karlsson; Gautier, Grégory; Tripodo, Claudio; Blank, Ulrich; Mion, Francesca; Pucillo, Carlo

doi:10.1002/eji.202048668

Cited by 10 publications

(12 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding IgA and IgM, stress decreases IgA+CD45+ cells, B cells, and plasmablasts (which could explain the general drop in total plasmablasts) but increases IgM+ B cells. However, the DSS model caused an increment in IgA+ cells and a drop in IgM+ 45 , contrary to our results. A feasible explanation relies on the disease stage simulated by our sub-chronic stress model.…”

Section: Discussioncontrasting

confidence: 99%

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

Martín-Hernández

Gutiérrez

González‐Prieto

et al. 2022

Sci Rep

View full text Add to dashboard Cite

The chronic inflammatory process that characterizes inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress is a potential trigger of clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. Hence, stress impact and the absence of sphingosine kinase 2 (Sphk2), an enzyme of S1P metabolism, were evaluated in the colon of mice after sub-chronic stress exposure. Here, we show that sub-chronic stress increased S1P in the mouse colon, possibly due to a decrease in its degradation enzymes and Sphk2. S1P accumulation could lead to inflammation and immune dysregulation reflected by upregulation of toll-like receptor 4 (TLR4) pathway, inhibition of anti-inflammatory mechanisms, cytokine-expression profile towards a T-helper lymphocyte 17 (Th17) polarization, plasmacytosis, decrease in IgA+ lymphoid lineage cells (CD45+)/B cells/plasmablasts, and increase in IgM+ B cells. Stress also enhanced intestinal permeability. Sphk2 knockout mice presented a cytokine-expression profile towards a boosted Th17 response, lower expression of claudin 3,4,7,8, and structural abnormalities in the colon. Intestinal pathophysiology should consider stress and S1P as modulators of the immune response. S1P-based drugs, including Sphk2 potentiation, represent a promising approach to treat IBD.

show abstract

Section: Discussioncontrasting

confidence: 99%

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

Martín-Hernández

Gutiérrez

González‐Prieto

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Previous work (5) established a prominent requirement for LTβR signaling in PP cDC2 and DN cDC homeostasis, and we confirmed Tph1 + mast cells promote cDC2 positioning in SED and the IgA response Mast cells have been implicated as a source of the GPR35 ligand 5-HIAA at sites of inflammation (11,13,22). Moreover, mast cells can augment intestinal IgA responses during inflammation (23). We therefore investigated the impact of mast cell deficiency on the PP IgA response.…”

Section: Gpr35 In Cdcs Is Required For Pp and Intestinal Igasupporting

confidence: 65%

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

De Giovanni,

Vykunta,

Biram

et al. 2024

Sci. Immunol.

View full text Add to dashboard Cite

Peyer’s patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA + germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell–deficient mice had reduced PP cDC2s and IgA + cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell–guided positioning of GPR35 + cDC2s in the PP SED supports induction of intestinal IgA responses.

show abstract

“…Pucillo and colleagues further reported that the CD40/CD40Lmediated MC/B cell contact, together with IL-6 secretion by MCs differentiates B cells to CD138 + plasma cells and IgA secretion [114]. The same group demonstrated the MC/B cell crosstalk in the inflamed colon of inflammatory bowel disease (IBD) patients and by using MC depleted mice, confirmed in vivo, a role for MCs in the control of B cell distribution in the gut, and in the increased IgA production upon dextran sulfate sodium (DSS)-colitis [119]. In vitro, MCs regulated splenic B cells, while peritoneal B cells were unresponsive but skewed the MCs to increased IL33 receptor expression and TNF production [116].…”

Section: Functions In B Cell Activationmentioning

confidence: 83%

Mast Cell Functions Linking Innate Sensing to Adaptive Immunity

Katsoulis‐Dimitriou

Kotrba

Voß

et al. 2020

Preprint

View full text Add to dashboard Cite

Although Mast cells are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs do not only play an important role in initiating innate immune responses, but also influence the onset, kinetic and amplitude of the adaptive arm of immunity, or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T cell activation by direct interaction or indirectly by modifying properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and the adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.

show abstract

Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine

Cited by 10 publications

References 38 publications

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

Mast Cell Functions Linking Innate Sensing to Adaptive Immunity

Contact Info

Product

Resources

About