The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers

Round 1

Reviewer 1 Report

This review demonstrates the role of mast cells in the homeostasis of immune system. Generally, this manuscript is well organized and provides sufficient information about mast cells in the modulation of immune responses to cancers and infections. However, there are several minor points should be noticed. 

Minor points:

1. line 54 to 56, the authors mention that autoimmune diseases including atherosclerosis, allograft rejection, neoplasia, rheumatoid arthritis. However, among these diseases, only rheumatoid arthritis belongs to autoimmune disease. Therefore, this sentence should be rephrased.
2. Authors also demonstrate the promoting or inhibitory effects of mast cells in different cancers, thus, this part should be included in the title of this manuscript, too.
3. The underline in the words, such as line 116-117 and table 2 and 5, should be removed. 
4. Line 574-576, ref. 85 did not demonstrate the role of mast cells in the production of proinflammatory cytokines in psoriasis, therefore, authors should cite paper which describe the role of mast cells in the psoriasis.
5. In the paragraph discuss about IL-37, several novel studies demonstrated about the association between mast cells and IL-37, such as Int J Mol Sci. 2020 Jun 16;21(12):4297, Int J Mol Sci. 2021 Jul 28;22(15):8076, Int Immunopharmacol. 2020 Jun;83:106476, Crit Rev Immunol. 2019;39(4):267-274, should be included in this paragraph.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

Thank you for all comments. Below you will find the Authors' replay to Editor's and Reviewers' comments. 

Dear Liliana Carmen Tatar
Assigned Editor,

Thank you for the comments. We have gone over the entire revision and corrected the writing style where applicable. The Authors’ correction according to the Editor’s and Reviewers’ comments was included in the revised manuscript (marked in yellow in Track Changes using MS Word). Authors’ answers to Editor's and Reviewers’ comments are included below in the original letter form the Editor (marked in black in Table below). The suitable letter was prepared below and the Author’s answers are indicated in red. Additional changes introduced by the Authors were marked in yellow. English (British spelling was used) and the style of manuscript was corrected and marked in the proofreading program in the original Ms.

Regards,

Monika Staniszewska

Corresponding author

Editor's original letter:

(I)  Please revise your manuscript according to the referees’ comments and upload the revised file within 5 days.

(II) Please use the version of your manuscript found at the above link for your revisions.
(III) Any revisions made to the manuscript should be marked up using the “Track Changes” function if you are using MS Word/LaTeX, such that changes can be easily viewed by the editors and reviewers.
(IV) Please provide a short cover letter detailing your changes for the editors’ and referees’ approval.

If one of the referees has suggested that your manuscript should undergo extensive English revisions, please address this issue during revision. We propose that you use one of the editing services listed at
https://www.mdpi.com/authors/english or have your manuscript checked by a native English-speaking colleague.
Please do not hesitate to contact us if you have any questions regarding the revision of your manuscript or if you need more time. We look forward to hearing from you soon.

Rev#1

This review demonstrates the role of mast cells in the homeostasis of immune system. Generally, this manuscript is well organized and provides sufficient information about mast cells in the modulation of immune responses to cancers and infections. However, there are several minor points should be noticed. 

Minor points:

Rev2

This article reviews the diverse roles of mast cells. Mast cells are long-lived, tissue-resident cells, and the authors specifically discuss their role in immune homeostasis and in host defense against pathogens. The authors summarize the multifaceted nature of mast cells, which can contribute to host health, but also have negative effects on host tissues, in the following sections.

The authors summarize the types of Pattern Recognition Receptors that mast cells possess, their ligands, and the signaling pathways within mast cells after recognition. These responses result in pathogen elimination in the case of a moderate inflammatory response. On the other hand, mast cells are involved in tissue destruction in many inflammatory diseases because they release chemokines that recruit leukocyte subtypes that are harmful to the host tissue.

The synthesis process of secretory granules of mast cells, their contents, and their effects are described.

The authors also review in detail the effects of cytokines, chemokines, and secretory granules released from activated mast cells on non-mast immune cells and tissue cells.

While mast cells exhibit anticancer activity, they can also promote tumor invasion by inducing angiogenesis.

 This paper introduces the dynamics and functions of mast cells, which could be analyzed by the existence of a mast cell-deficient mouse model.

The multifaceted mast cell actions are summarized by drawing on a vast amount of literature, but much of the information has already been described in other reviews.

However, it is a carefully written review and the mention of mast cell-neuron interaction is new and quite interesting.

A few minor revisions are listed below.

Reviewer 2 Report

This article reviews the diverse roles of mast cells. Mast cells are long-lived, tissue-resident cells, and the authors specifically discuss their role in immune homeostasis and in host defense against pathogens. The authors summarize the multifaceted nature of mast cells, which can contribute to host health, but also have negative effects on host tissues, in the following sections.

　The authors summarize the types of Pattern Recognition Receptors that mast cells possess, their ligands, and the signaling pathways within mast cells after recognition. These responses result in pathogen elimination in the case of a moderate inflammatory response. On the other hand, mast cells are involved in tissue destruction in many inflammatory diseases because they release chemokines that recruit leukocyte subtypes that are harmful to the host tissue.

The synthesis process of secretory granules of mast cells, their contents, and their effects are described.

The authors also review in detail the effects of cytokines, chemokines, and secretory granules released from activated mast cells on non-mast immune cells and tissue cells.

　While mast cells exhibit anticancer activity, they can also promote tumor invasion by inducing angiogenesis.

 This paper introduces the dynamics and functions of mast cells, which could be analyzed by the existence of a mast cell-deficient mouse model.

The multifaceted mast cell actions are summarized by drawing on a vast amount of literature, but much of the information has already been described in other reviews.

However, it is a carefully written review and the mention of mast cell-neuron interaction is new and quite interesting.

A few minor revisions are listed below.

There is a typographical error in p15, line 493; IL-1ra. 

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

Thank you for all comments. Below you will find the authors' answers to Editor's and Reviewers' comments. 

Dear Liliana Carmen Tatar
Assigned Editor,

Thank you for the comments. We have gone over the entire revision and corrected the writing style where applicable. The Authors’ correction according to the Editor’s and Reviewers’ comments was included in the revised manuscript (marked in yellow in Track Changes using MS Word). Authors’ answers to Editor's and Reviewers’ comments are included below in the original letter form the Editor (marked in black in Table below). The suitable letter was prepared below and the Author’s answers are indicated in red. Additional changes introduced by the Authors were marked in yellow. English (British spelling was used) and the style of manuscript was corrected and marked in the proofreading program in the original Ms.

Regards,

Monika Staniszewska

Corresponding author

Editor's original letter:

(I)  Please revise your manuscript according to the referees’ comments and upload the revised file within 5 days.

(II) Please use the version of your manuscript found at the above link for your revisions.
(III) Any revisions made to the manuscript should be marked up using the “Track Changes” function if you are using MS Word/LaTeX, such that changes can be easily viewed by the editors and reviewers.
(IV) Please provide a short cover letter detailing your changes for the editors’ and referees’ approval.

If one of the referees has suggested that your manuscript should undergo extensive English revisions, please address this issue during revision. We propose that you use one of the editing services listed at
https://www.mdpi.com/authors/english or have your manuscript checked by a native English-speaking colleague.
Please do not hesitate to contact us if you have any questions regarding the revision of your manuscript or if you need more time. We look forward to hearing from you soon.

Rev#1

This review demonstrates the role of mast cells in the homeostasis of immune system. Generally, this manuscript is well organized and provides sufficient information about mast cells in the modulation of immune responses to cancers and infections. However, there are several minor points should be noticed. 

Minor points:

Rev2

This article reviews the diverse roles of mast cells. Mast cells are long-lived, tissue-resident cells, and the authors specifically discuss their role in immune homeostasis and in host defense against pathogens. The authors summarize the multifaceted nature of mast cells, which can contribute to host health, but also have negative effects on host tissues, in the following sections.

The authors summarize the types of Pattern Recognition Receptors that mast cells possess, their ligands, and the signaling pathways within mast cells after recognition. These responses result in pathogen elimination in the case of a moderate inflammatory response. On the other hand, mast cells are involved in tissue destruction in many inflammatory diseases because they release chemokines that recruit leukocyte subtypes that are harmful to the host tissue.

The synthesis process of secretory granules of mast cells, their contents, and their effects are described.

The authors also review in detail the effects of cytokines, chemokines, and secretory granules released from activated mast cells on non-mast immune cells and tissue cells.

While mast cells exhibit anticancer activity, they can also promote tumor invasion by inducing angiogenesis.

 This paper introduces the dynamics and functions of mast cells, which could be analyzed by the existence of a mast cell-deficient mouse model.

The multifaceted mast cell actions are summarized by drawing on a vast amount of literature, but much of the information has already been described in other reviews.

However, it is a carefully written review and the mention of mast cell-neuron interaction is new and quite interesting.

A few minor revisions are listed below.