Mucosal SIgA Enhancement: Development of Safe and Effective Mucosal Adjuvants and Mucosal Antigen Delivery Vehicles

Kunisawa, Jun; McGhee, Jerry R.; Kiyono, Hiroshi

doi:10.1007/978-0-387-72232-0_14

Cited by 11 publications

(17 citation statements)

References 247 publications

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“…[22][23][24] S-IgA, a hallmark antibody principally produced at mucosal sites, plays an important role in the creation of immunologic surveillance and homeostasis at mucosa by abolishing pathogenic microbial infections and establishing symbiosis with commensal flora. 25,26 One major source of S-IgA is B2 B cells derived from the common mucosal immune system (CMIS) that links inductive (eg, Peyer patches and isolated lymphoid follicles) and effector tissues (eg, lamina propria region). These B2 B cells have been shown to play a key role in the induction of TD antigen-specific S-IgA.…”

Section: Introductionmentioning

confidence: 99%

Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production

Kunisawa

Kurashima

Gohda

et al. 2007

Blood

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106

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Sphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation of lymphocyte emigration from organized lymphoid tissues such as the peripheral lymph nodes and thymus, but its immunologic role in unorganized and diffused tissues remains to be elucidated. Here we show that the trafficking of peritoneal B cells is principally regulated by S1P. All peritoneal B cells including B1a, B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus, treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance of peritoneal B cells by inhibiting both their emigration from parathymic lymph nodes and their recirculation from the blood into the peritoneal cavity without affecting their progenitor populations. These changes did not affect natural plasma antibody production or phosphorylcholine (PC)-specific antibody production in serum after peritoneal immunization with heatkilled Streptococcal pneumoniae (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural intestinal secretory IgA production without affecting the expression of J-chain and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of PC-specific fecal IgA responses after oral immunization with R36A. These findings point to a pivotal role for S1P in connect IntroductionSphingosine 1-phosphate (S1P) has been identified as an important molecule in the regulation of lymphocyte egress from the organized lymphoid structures including the thymus and secondary lymphoid organs. 1,2 At present, 5 kinds of S1P receptors have been identified, each sharing S1P as its ligand but associating with a different type of G protein, resulting in a distinct signal transduction. 3 Accumulating evidence has demonstrated that type 1 S1P receptor (S1P1) is preferentially expressed on lymphocytes, and their expression is closely regulated by lymphocyte activation or development, which determines lymphocyte emigration from secondary lymph organs as well as the thymus. 4,5 FTY720, 2-amino-2-[2-(4-octylphenyl)-ethyl] propane-1,3-diol hydrochloride, acts as an agonist for S1P receptors, except the type 2 S1P receptor (S1P2). 6-8 FTY720 blocks S1P-mediated signaling by inducing internalization of receptors. 4,9 Therefore, treatment with FTY720 decreased the number of circulating lymphocytes in both blood and lymph, by inhibiting their emigration from the secondary lymphoid organs and thymus and by modulating integrin-dependent lymphocyte homing into peripheral lymph nodes. [10][11][12] Several lines of evidence have revealed that S1P also regulates B-cell distribution in the spleen, suggesting that FTY720 can impair plasma antibody production, especially against T-dependent (TD) antigen due to the abolishment of germinal center formation. [13][14][15] In addition, a recent study revealed that S1P plays an important role in the determination of plasma cell tropism to bone marrow. 16 Despite the substantial evidence pointing to the role of S1P in the regulation of lymphocyte trafficking at the syst...

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Section: Introductionmentioning

confidence: 99%

Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production

Kunisawa

Kurashima

Gohda

et al. 2007

Blood

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…IgG) [91] (also see the article by Belyakov and colleagues in this issue). Because mucosal immunization can effectively induce both layers of antigen-specific immunity, it has been considered that mucosal vaccination is an ideal strategy for the global control of mucosal infectious diseases [91]. In general, thanks to the above-described elegance of the imprinting system for tissue tropism of mucosally activated lymphocytes, the antigen-specific humoral and cellular immune responses induced by mucosal immunization most effectively occur at the site of antigen-deposited mucosal tissues with some mobility to the other mucosa-associated tissues.…”

Section: Mucosal Lymphocyte Traffickingmentioning

confidence: 89%

“…Understanding the molecular and cellular functions of the mucosal immune system associated with the aero-digestive tract has allowed us to create a general consensus that nasal or oral administration is an effective regimen for the induction of localized antigen-specific mucosal immune responses mediated by both S-IgA and CTL as well as systemic immune responses (e.g. IgG) [91] (also see the article by Belyakov and colleagues in this issue). Because mucosal immunization can effectively induce both layers of antigen-specific immunity, it has been considered that mucosal vaccination is an ideal strategy for the global control of mucosal infectious diseases [91].…”

Section: Mucosal Lymphocyte Traffickingmentioning

confidence: 98%

“…To accomplish this goal, a plant-based vaccine is considered to be one attractive strategy, because plants can be used as natural bioreactors and transporters of vaccine antigens. Progress in plant genetic technology has enabled the development of plant-based oral subunit vaccines [91]. Among the several plant-based vaccines developed so far, a rice-based oral vaccine (or MucoRice TM ) has recently attracted interest as a vaccine production and delivery system because of its practical advantages [101].…”

Section: Reviewmentioning

confidence: 99%

“…Ulex europaeus agglutinin-1 (UEA-1) [102,103] and YQC-SYTMPHPPV [104]] or microbial invasion molecules known to target M cells (e.g. reovirus s1 protein and Yersinia-derived invasin) into the vaccine [91,105] have been examined as the cell-targeted delivery vehicles for nasal or oral vaccines, but their binding to other neighboring cells (e.g. UEA-1 binding to goblet cells [106]) has hampered their effective delivery of antigens to M cells.…”

Section: Reviewmentioning

confidence: 99%

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